| 1. |
- Adner, Mikael, et al.
(författare)
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Upregulation of a non-ETA receptor in human arteries in vitro
- 1995
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 26:Suppl. 3, s. 314-316
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Tidskriftsartikel (refereegranskat)abstract
- Receptor turnover may be a crucial part in the physiology of endothelin (ET). Incubation of vessel segments could be a possible method to demonstrate this. The aim was to study contractile responses of human omental arteries to different ET agonists at various periods after incubation at 37 degrees C in 5% CO2 and air. The maximum effect (Emax; percentage of contraction to 60 mM K+ buffer solution) and the potency of ET-1 were unaltered (pD2 = 8.82 +/- 0.06). The selective ETB agonist IRL 1620 demonstrated a negligible Emax in nonincubated segments (2.4 +/- 0.9%). After only 1 day of incubation the Emax was 51 +/- 23%, and it reached 114 +/- 53% after 5 days. The pD2 of IRL 1620 was stable throughout the incubation time (7.23 +/- 0.08). ET-3 showed a moderate Emax in nonincubated segments (55 +/- 18%), with a pD2 of 6.68 +/- 0.24. However, subsequent incubation revealed an increase of pD2 to 8.60 +/- 0.20 on the fifth day. The maximum contraction increased to 206 +/- 44%; this is equal to the contraction obtained in paired experiments with ET-1 (215 +/- 18%). These findings indicate modulation of endothelin receptor expression after incubation of vessel segments, and suggest the gradual appearance of a non-ETA receptor.
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| 2. |
- Bergh, Niklas, 1979, et al.
(författare)
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Efficacy and safety of clopidogrel versus ticagrelor as part of dual antiplatelet therapy in acute coronary syndrome - a systematic review and meta-analysis.
- 2022
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Ingår i: Journal of cardiovascular pharmacology. - 1533-4023. ; 79:5, s. 620-631
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and safety of clopidogrel compared with ticagrelor as part of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome is reviewed. PubMed, Embase, the Cochrane Library, Medline, and HTA databases were searched (Sep 2nd 2020) for randomised controlled trials (RCTs). ACS patients subjected to clopidogrel or ticagrelor as part of DAPT were included. Pooled risk-differences were estimated using random-effects meta-analyses, and certainty of evidence was assessed according to GRADE. In ACS patients subjected to DAPT, the pooled risk difference for all-cause mortality was 0·6% (-0·03% to 1·3%; I2: 18%); cardiovascular mortality: 0·6% (0·01% to 1·1%; I2: 22%); MI: 0·9% (0·4% to 1·3%; I2: 5%); stent thrombosis: 0·7% (0·4 to 1·1%; I2: 0%); clinically significant bleeding: -1·9% (-3·7% to -0·2%; I2: 69%); major bleeding: -0·9% (-1·6% to -0·1%; I2: 32%); and dyspnea: -5·8% (-7·7% to -3·8%; I2: 63%). In the subgroup of older patients there were no differences between the comparison groups regarding all-cause mortality, CV mortality and MI, whereas the risk of clinically significant bleeding and major bleeding was lower in the clopidogrel group, -5·9% (-11 to -0·9%, 1 RCT) and -2·4% (-4·4% to -0·3%, I2: 0%), respectively. Compared with ticagrelor, clopidogrel may result in little or no difference regarding all-cause mortality. In older patients, clopidogrel may be slightly less efficient in reducing the risk of cardiovascular mortality and MI. Clopidogrel results in a reduced risk of bleedings and dyspnea.
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| 3. |
- Bredie, S J, et al.
(författare)
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No Significant Effect of Ginkgo Biloba Special Extract EGb 761 in the Treatment of Primary Raynaud's Phenomenon: A Randomized Controlled Trial
- 2012
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 59:3, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Medicinal treatment of vasospastic Raynaud phenomenon is limited to primarily vasodilator medicines.OBJECTIVE:To explore the possible beneficial effects and tolerability of 120 mg two times a day of Ginkgo Biloba special extract EGb 761 in patients suffering from Raynaud disease (RD) (primary Raynaud phenomenon).METHODS:In a placebo-controlled, double-blind, pilot study, 41 patients with RD were randomized to either the active treatment group (EGb 761, n = 21) or placebo group for 10 weeks, after an initial 2-week run-in phase. The primary efficacy variables were self-reported changes of the frequency, duration, and severity of vasospastic attacks between the placebo-controlled run-in phase and the end of the study.RESULTS:Most of the patients were female, and both groups were perfectly matched with respect to demographic characteristics. The frequency of daily attacks reduced from 3.6 ± 2.3 to 2.4 ± 2.6 (-33%) in the EGb 761 group and from 2.9 ± 2.0 to 2.0 ± 1.8 (-31%) in the placebo group with no significant difference according to the ordinary least squares test (P = 0.3564). Furthermore, no significant differences were found with respect to the duration and severity of vasospastic attacks between the EGb 761 and placebo groups (P = 0.4392 and P = 0.7187, respectively). In all, 17 adverse events (AEs) were reported, 6 AEs from 5 patients in the EGb 761 group and 11 AEs from 8 patients in the placebo group. Serious AEs did not occur.CONCLUSION:EGb 761 treatment showed an excellent safety profile in patients with RD but could not demonstrate a statistically significant reduction in clinically relevant symptoms compared with placebo.
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| 4. |
- Christensen, Simon Topp, et al.
(författare)
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Exploration of Physiological and Pathophysiological Implications of miRNA-143 and miRNA-145 in Cerebral Arteries
- 2019
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 74:5, s. 409-419
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Tidskriftsartikel (refereegranskat)abstract
- Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke with a high short-term mortality rate which leads to cognitive impairments that reduce the quality of life of the majority of patients. The miRNA-143/145 cluster is highly expressed in vascular smooth muscle cells (VSMC) and has been shown to be necessary for differentiation and function, as well as an important determinant for phenotypic modulation/switching of VSMCs in response to vascular injury. We aimed to determine whether miRNA-143 and miRNA-145 are important regulators of phenotypical changes of VSMCs in relation to SAH, as well as establishing their physiological role in the cerebral vasculature. We applied quantitative PCR to study ischemia-induced alterations in the expression of miRNA-143 and miRNA-145, for rat cerebral vasculature, in an ex vivo organ culture model and an in vivo SAH model. To determine the physiological importance, we did myograph studies on basilar and femoral arteries from miRNA-143/145 knockout mice. miRNA-143 and miRNA-145 are not upregulated in the vasculature following our SAH model, despite the upregulation of miR-145 in the organ culture model. Regarding physiological function, miRNA-143 and miRNA-145 are very important for general contractility in cerebral vessels in response to depolarization, angiotensin II, and endothelin-1. Applying an anti-miRNA targeting approach in SAH does not seem to be a feasible approach because miRNA-143 and miRNA-145 are not upregulated following SAH. The knockout mouse data suggest that targeting miRNA-143 and miRNA-145 would lead to a general reduced contractility of the cerebral vasculature and unwanted dedifferentiation of VSMCs.
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| 5. |
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| 6. |
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| 7. |
- Ekelund, Ulf, et al.
(författare)
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Effects of the combined ETA and ETB receptor antagonist PD145065 on arteries, arterioles, and veins in the cat hindlimb
- 1995
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 26:Suppl. 3, s. 211-213
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe in quantitative terms the effects of ETA and ETB receptor blockade on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 microns), small arterioles (< 25 microns), and veins in the cat gastrocnemius muscle in vivo. In the muscle vascular bed, the combined ETA and ETB receptor antagonist PD145065 (1 mg/kg/min, intra-arterially) abolished the biphasic vascular responses (dilatation followed by constriction) to both ET-1 (0.4 microgram/kg/min, intra-arterially) and to the selective ETB receptor agonist IRL1620 (3.2 micrograms/kg/min, intra-arterially). In the cat femoral artery and vein in vitro, PD145065 competitively inhibited the contractile responses to both ET-1 and IRL1620. The contractile response to the latter agonist could be evoked only after long-term incubation of the vessels (37 degrees C for 5 days). These results indicate that PD145065 is a potent antagonist at both ETA and ETB receptors in vivo and in vitro. Therefore, this antagonist may prove useful for elucidating the possible physiologic and/or pathophysiologic roles of the endothelins. For example, it was shown that PD145065 had no effect on vascular tone in the resting state, indicating no role for the endothelins in the regulation of basal vascular tone in cat skeletal muscle.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Ferone, Emma, et al.
(författare)
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Current treatment and immunomodulation strategies in Acute Myocarditis.
- 2024
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Ingår i: Journal of cardiovascular pharmacology. - 1533-4023.
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Tidskriftsartikel (refereegranskat)abstract
- Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarise the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis.
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| 12. |
- Hansen, Ole, et al.
(författare)
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Effects of carvedilol on the metabolic, hemodynamic, and electrocardiographic responses to increased plasma epinephrine in normal subjects
- 1994
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 24:6, s. 853-859
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Tidskriftsartikel (refereegranskat)abstract
- To study the effects of the new vasodilating beta-blocking agent carvedilol on a variety of metabolic, hemodynamic, and ECG parameters of importance for the clinical outcome of acute myocardial infarction (AMI), we infused epinephrine (EPI) in healthy male volunteers on two separate occasions to serum concentrations of the same level reached in AMI. Before the EPI infusions, the volunteers were pretreated for 2 weeks with either carvedilol or placebo in randomized order. EPI caused significant decreases in serum levels: S-potassium (0.62 mM), S-magnesium (0.07 mM), S-calcium (0.12 mM), and S-phosphate (0.26 mM). After pretreatment with carvedilol, the decreases in S-calcium and S-phosphate were partly prevented and those in S-potassium and S-magnesium were completely inhibited. Short-term treatment with carvedilol significantly decreased S-insulin and serum C-peptide and significantly attenuated the EPI-induced increase in B-glucose observed after placebo. The EPI infusion significantly increased serum concentrations of free fatty acids and glycerol. These increases were significantly attenuated by carvedilol, whereas carvedilol had no significant affects of a variety of other lipid variables. EPI infusion caused a significant (p < 0.01) increase in systolic blood pressure (SBP) from 124.8 +/- 8.1 to 135.8 +/- 12.5 mm Hg and an increase in heart rate (HR) from 71.0 +/- 11.5 to 77.2 +/- 12.2, resulting in a significant increase in rate-pressure product (RPP). This estimate of cardiac work was significantly (p < 0.05) reduced by pretreatment with carvedilol.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 13. |
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| 14. |
- Hill, JA, et al.
(författare)
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Medical Misinformation: Vet the Message!
- 2019
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Ingår i: Journal of cardiovascular pharmacology. - 1533-4023. ; 73:2, s. 61-62
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Holmgren, Anton, et al.
(författare)
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Inhibition of angiotensin II-induced contraction by losartan in human coronary arteries
- 1998
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 32:4, s. 662-664
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Tidskriftsartikel (refereegranskat)abstract
- The in vitro effects of angiotensin II (Ang II) in human vessels are not well studied. The development of specific Ang II-receptor antagonists has made it possible to delineate more carefully the receptor mechanisms involved. The objective of this study was twofold: to investigate the effect of Ang II on human coronary arteries and to study the effects of angiotensin II type 1 receptor blockade with losartan. The setting was contractile experiments with ring segments of coronary arteries. We observed that Ang II is a vasoconstrictor of human coronary arteries, with a pEC50 value of 9.26 +/- 0.22 and Emax of 68.7 +/- 9.61% of potassium-induced contraction. Losartan (10-100 nM) shifted the concentration-response curve of Ang II to the right, with pEC50 values of 7.64 +/- 0.10 and 7.00 +/- 0.15, respectively (p = 0.001), demonstrating the antagonistic properties of losartan. We also noted a decreased maximal response to Ang II after incubation of losartan, with Emax of 51.1 +/- 7.08% and 41.9 +/- 4.70% (p = 0.05), respectively. In conclusion, this is the first report describing the contractile effect of Ang II and the antagonizing effects of losartan in isolated human coronary arteries.
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| 16. |
- Holmgren, Christina M, et al.
(författare)
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Changes in Medication Preceding Out-of-hospital Cardiac Arrest Where Resuscitation Was Attempted
- 2014
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Ingår i: Journal of Cardiovascular Pharmacology. - : Lippincott Williams & Wilkins. - 0160-2446 .- 1533-4023. ; 63:6, s. 497-503
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe recent changes in medication preceding out-of-hospital cardiac arrest (OHCA) where resuscitation was attempted. Methods: OHCA victims were identified by the Swedish Cardiac Arrest Register and linked by means of their unique 10-digit personal identification numbers to the Prescribed Drug Register. We identified new claimed prescriptions during a 6-month period before the OHCA compared with those claimed in the period 12 to 18 months before. The 7-digit Anatomical Therapeutical Chemical codes of individual drugs were used. The study period was November 2007-January 2011. Results: OHCA victims with drugs were (1) older than those who did not claim any drugs in any period (70 +/- 16 years vs. 54 +/- 22 years, P < 0.001), (2) more often women (34% vs. 20%, P < 0.001), and (3) had more often a presumed cardiac etiology (67% vs. 54%, P < 0.001). The OHCA victims were less likely to have ventricular tachycardia/ventricular fibrillation as the first recorded ;rhythm (26% vs. 33%, P < 0.001) or to survive 1 month (9% vs. 17%, P < 0.0001). New prescriptions were claimed by 5122 (71%) of 7243 OHCA victims. The most frequently claimed new drugs were paracetamol (acetaminophen) 10.3%, furosemide 7.8%, and omeprazole 7.6%. Of drugs known or supposed to cause QT prolongation, ciprofloxacin was the most frequent (3.4%) altogether; 16% had a new claimed prescription of a drug included in the "qtdrugs.org" lists. Conclusions: Most OHCA victims had new drugs prescribed within 6 months before the event but most often intended for diseases other than cardiac. No claims can be made as to the causality.
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| 17. |
- Jacobsson, Leif S., et al.
(författare)
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Antiatherosclerotic Effects of the Angiotensin-Converting Enzyme Inhibitors Captopril and Fosinopril in Hypercholesterolemic Minipigs
- 1994
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 24:4, s. 670-677
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the two angiotensin-converting enzyme (ACE) inhibitors captopril and fosinopril with regard to possible antiatherosclerotic effects in minipigs. Experimental hypercholesterolemia and atherosclerosis was produced in 33 minipigs of the Gottingen strain by an egg yolk/cholesterol-enriched diet for 1 year. One group (n = 11) was fed the atherogenic diet alone and served as a control. A second group (n = 11) received captopril (80 mg/kg/day) added to the atherogenic diet, and a third group (n = 11) was treated in the same manner but with fosinopril (8 mg/kglday). The drug treatments produced significant reduction in serum ACE activity associated with a reactive increase in plasma renin activity (PRA), but had only minor effects on plasma lipids and lipoproteins. At the end of the treatment period, all animals were killed and examined for degree of atherosclerosis. The percentage of atherosclerotic area in the abdominal aorta was significantly lower in both drug-treated groups as compared with controls. Furthermore, accumulation of cholesterol in the thoracic and abdominal aorta was inhibited by drug treatment. Finally, the percentage of intimal thickening in abdominal aorta was significantly reduced in the drug-treated groups. In conclusion, the ACE inhibitors captopril and fosinopril inhibited development of atherosclerosis in hypercholesterolemic minipigs.
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| 18. |
- Jekell, Andreas, et al.
(författare)
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Markers of inflammation, endothelial activation, and arterial stiffness in hypertensive heart disease and the effects of treatment : results from the SILVHIA study
- 2013
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 62:6, s. 559-566
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the contribution of blood pressure (BP), inflammation, and endothelial activation to the development of structural vascular and cardiac changes in hypertension. Furthermore, the effects of antihypertensive therapy were studied. We studied 114 patients with hypertension and left ventricular hypertrophy and 38 matched hypertensive subjects without cardiac hypertrophy and 38 normotensive subjects. The group with hypertension and cardiac hypertrophy were randomized to treatment with an angiotensin receptor blocker (irbesartan) or a beta-adrenergic receptor blocker (atenolol) for 48 weeks. Markers of inflammation (high-sensitive C-reactive protein, interleukin-6, leukocyte counts), vascular function (ambulatory aortic stiffness index, arterial compliance, and pulse pressure), and endothelial activation (E-selectin, intracellular adhesion molecule-1, vascular adhesion molecule-1) were assessed. Markers of inflammation and arterial stiffness were lowest in the normotensive group and highest in patients with hypertensive heart disease; endothelial markers were similar between groups. Inflammation was independently related to BP. Markers of arterial stiffness were independently related to BP and to a lesser extent to left ventricular mass. Antihypertensive treatment improved arterial compliance; inflammatory and endothelial markers remained unchanged. In conclusion, markers of inflammation and arterial stiffness are independently related to BP. Antihypertensive therapy seems to improve arterial stiffness, but effects on markers of inflammation and endothelial activation are small.
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| 19. |
- Johansson, B, et al.
(författare)
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Contractures induced by reversed Na+/Ca2+ exchange in rat portal vein: effects of calcium antagonists
- 1987
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 10:Suppl. 1, s. 75-81
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Tidskriftsartikel (refereegranskat)abstract
- Spontaneous electrical and mechanical activity was abolished in isolated preparations of rat portal vein by exposure to K+-free Krebs solution. This procedure probably also increased the intracellular [Na+] owing to interference with the active transmembrane Na+-K+ transport. Contractures could be induced under these conditions by lowering extracellular [Na+] from the control level of 144 to 17 mM using sucrose, TrisCl, or LiCl as NaCl substitutes. Contractile force depended on the type of substitute: sucrose greater than TrisCl greater than LiCl. These contractures are thought to be caused by influx of extracellular Ca2+ through the Na+/Ca2+ exchanger, which otherwise transports Ca2+ in the opposite direction at normal transmembrane Na+ gradient. The contractile response to low Na+ was rapidly and completely abolished in nominally Ca2+-free medium; it was strongly inhibited by 0.4 mM MnCl2 but was not affected by high concentrations of the organic calcium antagonists, felodipine (10(-6) M), verapamil (10(-5) M), or diltiazem (10(-5) M). We conclude that the Na+/Ca2+-exchanger is an effective pathway for Ca2+ transport over vascular smooth muscle cell membrane; this pathway is not blocked by calcium antagonists.
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| 20. |
- Kanukula, Raju, et al.
(författare)
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Does Co-administration of Antihypertensive Drugs and Statins Alter Their Efficacy and Safety? : A Systematic Review and Meta-analysis of Randomized Controlled Trials
- 2019
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 73:6, s. 352-358
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Forskningsöversikt (refereegranskat)abstract
- Antihypertensive drugs (AHTDs) and statins are frequently administered together, but there is uncertainty on whether the presence of one affects the main effects of the other. This systematic review and meta-analysis assessed the effects of coadministered AHTDs and statins on blood pressure (BP) and cholesterol. MEDLINE, Cochrane Central Register of Controlled Trials and drug regulatory agency websites were searched, until January 2018. Twelve double-blind randomized controlled trials that allocated adults with or without hypertension and/or hyperlipidemia (n = 4434) to fixed doses of AHTD alone, statin alone and both drugs together, for >= 4 weeks, were included. BP lowering was similar with AHTD + statin compared with AHTD alone [systolic BP -0.1 mm Hg, 95% confidence interval (CI), -1.0 to 0.8, and diastolic BP -1.0 mm Hg, 95% CI, -2.3 to -0.2]. AHTD + statin compared with statin alone resulted in small reduction in low-density lipoprotein cholesterol (-3.9 mg/dL, 95% CI, -6.1 to -1.7), and this effect was largely associated with co-administration of amlodipine and atorvastatin or rosuvastatin. There was no difference in safety outcomes. Overall, it can be concluded that there is no clinically important difference in the effects of AHTDs and statins whether used separately or together for reduction in BP and lowdensity lipoprotein cholesterol.
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| 21. |
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| 22. |
- Khedri, Masih, et al.
(författare)
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Statin Treatment Intensity, Discontinuation, and Long-Term Outcome in Patients With Acute Myocardial Infarction and Impaired Kidney Function
- 2023
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Ingår i: Journal of Cardiovascular Pharmacology. - : Wolters Kluwer. - 0160-2446 .- 1533-4023. ; 81:6, s. 400-410
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Tidskriftsartikel (refereegranskat)abstract
- Statin dosage in patients with acute myocardial infarction (AMI) and concomitant kidney dysfunction is a clinical dilemma. We studied discontinuation during the first year after an AMI and long-term outcome in patients receiving high versus low–moderate intensity statin treatment, in relation to kidney function. For the intention-to-treat analysis (ITT-A), we included all patients admitted to Swedish coronary care units for a first AMI between 2005 and 2016 that survived in-hospital, had known creatinine, and initiated statin therapy (N = 112,727). High intensity was initiated in 38.7% and low–moderate in 61.3%. In patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, 25% discontinued treatment the first year; however, the discontinuation rate was similar regardless of the statin intensity. After excluding patients who died, changed therapy, or were nonadherent during the first year, 84,705 remained for the on-treatment analysis (OT-A). Patients were followed for 12.6 (median 5.6) years. In patients with eGFR 30–59 mL/min, high-intensity statin was associated with lower risk for the composite death, reinfarction, or stroke both in ITT-A (hazard ratio [HR] 0.93; 95% confidence interval, 0.87–0.99) and OT-A (HR 0.90; 0.83–0.99); the interaction test for OT-A indicated no heterogeneity for the eGFR < 60 mL/min group (P = 0.46). Similar associations were seen for all-cause mortality. We confirm that high-intensity statin treatment is associated with improved long-term outcome after AMI in patients with reduced kidney function. Most patients with reduced kidney function initiated on high-intensity statins are persistent after 1 year and equally persistent as patients initiated on low–moderate intensity.
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| 23. |
- Lynch, Joseph J, et al.
(författare)
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Comparison of the Vasoconstrictor Effects of the Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist Telcagepant (MK-0974) and Zolmitriptan in Human Isolated Coronary Arteries.
- 2010
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 55:5, s. 518-521
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Tidskriftsartikel (refereegranskat)abstract
- Studies were conducted in human isolated coronary arteries to explore the vascular effects of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant, and to compare its coronary vasoconstrictive potential to that of zolmitriptan. KCl-precontracted coronary vessels were shown to relax to human alphaCGRP, with the CGRP-mediated vasorelaxation completely blocked with 30 muM telcagepant. In coronary vessels at basal tone, zolmitriptan caused a concentration-dependent contraction (pEC50 = 6.9 +/- 0.1, slope 0.94), with the greatest contraction obtained between 1-10 muM in most tissues. In contrast, telcagepant at concentrations up to 30 muM evoked no change in contractile tone. These findings suggest the potential for CGRP receptor antagonists to exert antimigraine efficacy in the absence of adverse effects on coronary tone.
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| 24. |
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| 25. |
- Millgård, Jonas, et al.
(författare)
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Divergent effects of different antihypertensive drugs on endothelium-dependent vasodilataiton in the human forearm
- 1998
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 32:3, s. 406-412
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Several studies indicated an abnormal endothelium-dependent vasodilation (EDV) in hypertensive patients, but no study has systematically investigated the effects of different pharmacologic classes of antihypertensive drugs on EDV. This study aimed to evaluate the effects of three different antihypertensive regimens [angiotensin-converting enzyme (ACE) inhibition, calcium channel blockade, and beta-blockade] on EDV when given locally in the forearm at a constant blood pressure. The increase in forearm blood flow (FBF) during local intraarterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation, EIDV) was measured in young, normotensive subjects by venous occlusion plethysmography, before and during concomitant local intraarterial infusion of any of the antihypertensive drugs. Without changing baseline FBF, enalaprilat (n=6, 2.4 mg/h) potentiated the increase in FBF induced by MCh [from 22.6+/-2.3 (SD) to 25.4+/-2.3 ml/min/100 ml tissue at 4 microg/min; p < 0.05], but the response to SNP was unchanged. Local intraarterial verapamil infusion (n=6), at a dose individually titrated to keep baseline FBF unchanged, did not alter the response to MCh infusion, whereas the response to SNP was potentiated. A higher dose of verapamil (n=6), which increased baseline FBF, increased both EDV and EIDV significantly in parallel (p < 0.05). The local propranolol infusion (n=6, 1.2 mg/h) attenuated the FBF response to MCh significantly (from 28.9+/-5.7 to 21.5+/-3.2 ml/min/100 ml tissue at 4 microg/min; p < 0.05), whereas both baseline FBF and the response to SNP were unchanged. In conclusion, this investigation showed that commonly used antihypertensive drugs affect endothelial vasodilator function in a different ways. ACE inhibition enhanced EDV, whereas a nonselective beta-blocker attenuated EDV. The calcium channel blocker, verapamil, improved both EDV and EIDV, probably by a direct effect on the vascular smooth-muscle cells.
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| 26. |
- Nilsson, Torun, et al.
(författare)
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Contractile effects of neuropeptide Y in human subcutaneous resistance arteries are mediated by Y1 receptors
- 1996
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 28:6, s. 764-768
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Tidskriftsartikel (refereegranskat)abstract
- The aim of our study was to determine the neuropeptide Y (NPY) receptor subtype responsible for the NPY-induced contraction of human subcutaneous (s.c.) resistance arteries. To elucidate this, we used (a) in vitro studies of NPY agonists: NPY, peptide YY (PYY), and Pro34NPY induced equally strong and equipotent concentration-dependent contractions of human s.c. resistance arteries, whereas NPY13-36 and NPY18-36 had no contractile effects; (b) in vitro studies using the NPY Y1-receptor antagonist, BIBP3226, which in nanomolar concentrations inhibited the contractile effect of NPY, causing a rightward shift of the concentration-response curve. pEC50 for NPY alone, 8.41 +/- 0.21; NPY + BIBP3226, 10 nM, 7.79 +/- 0.21; NPY + BIBP3226, 100 nM, 7.18 +/- 0.18; NPY + BIBP3226, 1 microM, 6.32 +/- 0.05 (n = 5-8). Schild-plot analysis indicated competitive antagonism: pA2 = 8.53 +/- 0.22 and slope = 0.99 +/- 0.14; (c) with reverse transcriptase-polymerase chain reaction (RT-PCR), we detected messenger RNA (mRNA) encoding the human NPY Y1 receptor and a splice variant of the receptor in human s.c. resistance arteries. On the basis of the agonists' potency order, the antagonistic effect of BIBP3226 on the NPY-induced contraction, and the presence of mRNA encoding the NPY Y1 receptor, we conclude that the NPY-induced contraction of human s.c. resistance arteries is mediated by NPY Y1 receptors.
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| 27. |
- Papp, Zoltan, et al.
(författare)
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Levosimendan Efficacy and Safety : 20 Years of SIMDAX in Clinical Use
- 2020
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Ingår i: Journal of Cardiovascular Pharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0160-2446 .- 1533-4023. ; 76:1, s. 4-22
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Tidskriftsartikel (refereegranskat)abstract
- Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.
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| 28. |
- Persson, Ingrid A L, et al.
(författare)
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Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers--a nutrigenomics perspective.
- 2011
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 57:1, s. 44-50
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests that cocoa from the bean of Theobroma cacao L. has beneficial effects on cardiovascular disease. The aim of this study was to investigate if cocoa extract and dark chocolate influence angiotensin-converting enzyme (ACE) and nitric oxide (NO) in human endothelial cells (in vitro) and in healthy volunteers (in vivo). ACE activity was analyzed with a commercial radioenzymatic assay and measured in human endothelial cells from umbilical veins (HUVEC) after 10 minutes of incubation with cocoa extract. NO was measured after 24 hours of incubation. ACE activity and NO were measured at baseline and after 30, 60, and 180 minutes in 16 healthy volunteers after a single intake of 75 g of dark chocolate containing 72% cocoa. Significant inhibition of ACE activity (P < 0.01) and significant increase of NO (P < 0.001) were seen in HUVEC. In the study subjects, a significant inhibition of ACE activity (mean 18%) 3 hours after intake of dark chocolate was seen, but no significant change in NO was seen. According to ACE genotype, significant inhibition of ACE activity was seen after 3 hours in individuals with genotype insertion/insertion and deletion/deletion (mean 21% and 28%, respectively). Data suggest that intake of dark chocolate containing high amount of cocoa inhibits ACE activity in vitro and in vivo.
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| 29. |
- Persson, Karin, et al.
(författare)
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Biphasic Response to Bradykinin in Isolated Porcine Iliac Arteries is Mediated by Bradykinin B1 and B2 Receptors
- 1998
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446 .- 1533-4023. ; 32:2, s. 306-313
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Tidskriftsartikel (refereegranskat)abstract
- Bradykinin-induced responses were studied in isolated porcine iliac arteries. Relaxation was endothelium dependent and seen at low concentrations (10-10-10-8 M) of bradykinin. It was inhibited by the bradykinin B2-receptor antagonist icatibant (HOE-140) and by the nitric oxide synthase inhibitor Nω-nitro-L-arginine. Bradykinin-induced relaxation was significantly potentiated by the kininase I carboxypeptidase inhibitor mergepta (10-6 M). Bradykinin (>10-7M) elicited contraction of preparations with or without endothelium. The contraction was abolished by indomethacin but was not affected by the thromboxane A2/prostaglandin H2-receptor antagonist SQ 29,548. Icatibant and the bradykinin B1-receptor antagonist desArg9[Leu8]bradykinin significantly decreased bradykinin-induced contraction regardless of endothelial function. The contraction also was decreased by treatment with mergepta. The bradykinin B1-receptor agonist desArg9-bradykinin contracted endothelium-denuded arterial strips. This contraction was significantly decreased by desArg9 [Leu8] bradykinin but not by icatibant. The desArg9-bradykinin-induced contraction also was inhibited by the protein-synthesis inhibitor cycloheximide. Neither bradykinin-induced relaxation nor contraction was affected by the ACE inhibitors enalaprilat or cilazaprilat. In conclusion, bradykinin-induced relaxation of isolated porcine iliac arteries was mediated by endothelial bradykinin B2 receptors and mainly nitric oxide. Bradykinin-induced contraction was endothelium independent, indomethacin sensitive, and probably mediated by bradykinin B1 (inducible) and B2 receptors located in the vascular smooth-muscle layer. Kininase I carboxypeptidase, and not ACE, is the main enzyme responsible for bradykinin degradation in these vessels.
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| 30. |
- Rehnström, Mimmi, et al.
(författare)
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Ovariectomy Reduces Vasocontractile Responses of Rat Middle Cerebral Arteries After Focal Cerebral Ischemia
- 2022
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 79:1, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Effects of sex hormones on stroke outcome are not fully understood. A deleterious consequence of cerebral ischemia is upregulation of vasoconstrictor receptors in cerebral arteries that exacerbate stroke injury. Here, we tested the hypothesis that female sex hormones alter vasocontractile responses after experimental stroke in vivo or after organ culture in vitro, a model of vasocontractile receptor upregulation. Female rats with intact ovaries and ovariectomized (OVX) females treated with 17β-estradiol, progesterone, or placebo were subjected to transient, unilateral middle cerebral artery occlusion followed by reperfusion (I/R). The maximum contractile response, measured my wire myography, in response to the endothelin B receptor agonist sarafotoxin 6c was increased in female arteries after I/R, but the maximum response was significantly lower in arteries from OVX females. Maximum contraction mediated by the serotonin agonist 5-carboxamidotryptamine was diminished after I/R, with arteries from OVX females showing a greater decrease in maximum contractile response. Contraction elicited by angiotensin II was similar in all arteries. Neither estrogen nor progesterone treatment of OVX females affected I/R-induced changes in endothelin B- and 5-carboxamidotryptamine-induced vasocontraction. These findings suggest that sex hormones do not directly influence vasocontractile alterations that occur after ischemic stroke; however, loss of ovarian function does impact this process.
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| 31. |
- Scheiman, JM, et al.
(författare)
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Esomeprazole for prevention and resolution of upper gastrointestinal symptoms in patients treated with low-dose acetylsalicylic acid for cardiovascular protection : the OBERON trial.
- 2013
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Ingår i: Journal of Cardiovascular Pharmacology. - : Lippincott Williams & Wilkins. - 0160-2446 .- 1533-4023. ; 61:3, s. 250-257
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Tidskriftsartikel (refereegranskat)abstract
- Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P < 0.0001) in those treated with esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P < 0.0001), age >70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.
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| 32. |
- Sirsjö, Allan, et al.
(författare)
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Deficiency of nitric oxide synthase 2 results in increased neointima formation in a mouse model of vascular injury
- 2003
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Ingår i: Journal of Cardiovascular Pharmacology. - : Lippincott Williams & Wilkins. - 0160-2446 .- 1533-4023. ; 41:6, s. 897-902
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Tidskriftsartikel (refereegranskat)abstract
- Restenosis frequently occurs after arterial interventions. The inducible form of nitric oxide synthase (NOS2) may both promote and inhibit neointima formation. This study investigated the role of NOS2 for neointima formation in a mouse model of carotid artery injury. The common carotid artery was ligated in anesthetized mice. Homozygous NOS2 knockout mice were compared with wild-type B6/129 mice or wild-type mice treated with the pharmacologic NOS2 inhibitor aminoguanidine given orally daily after ligation (n = 6-8 in each group). Vessels were harvested for quantification of lesion size 4 weeks later, or serially after ligation for tissue analysis. mRNA for NOS2 increased 1-4 days after ligation of the carotid artery. Cell proliferation could be visualized with an antibody against proliferating cell nuclear antigen. An intimal smooth muscle cell layer, confirmed by an alpha-actin antibody, was observed in the lumen 4 weeks after injury. Inhibition of NOS2 by either pharmacologic or genetic approaches tended to increase the area of intima formation (P = 0.13 or P less than 0.05, respectively) and increased the intima/media ratio (P = 0.14 and P less than 0.01, respectively). Inhibition of NOS2 by two different approaches increased neointima formation in a mouse model of mechanical vessel injury, indicating that the NOS2 expressed in the injured vessel wall is beneficial.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Toivonen, Lauri, et al.
(författare)
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A Randomized Invasive Cardiac Electrophysiology Study of the Combined Ion Channel Blocker AZD1305 in Patients After Catheter Ablation of Atrial Flutter
- 2010
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Ingår i: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. - : Raven Press Publishers. - 0160-2446 .- 1533-4023. ; 56:3, s. 300-308
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study assessed the cardiac electrophysiological and hemodynamic effects of an intravenous infusion of the combined ion channel blocker AZD1305. Methods: After successful ablation of atrial flutter, patients were randomized to receive placebo (n = 12) or AZD1305 (n = 38) in 4 ascending dose groups. Electrophysiological and hemodynamic measurements were performed before and commencing 20 minutes after start of infusion. Results: Left atrial effective refractory period increased dose and the primary outcome measure increased dose and plasma concentration dependently, with a mean increase of 55 milliseconds in dose group 3. There was a corresponding increase in right atrial effective refractory period of 84 milliseconds. The right ventricular effective refractory period and the paced QT interval also increased dose and concentration dependently, by 59 and 70 milliseconds, respectively, in dose group 3. There were indications of moderate increases of atrial, atrioventricular nodal, and ventricular conduction times. No consistent changes in intracardiac pressures were observed, but there was a small transient decrease in systolic blood pressure. Adverse events were consistent with the study population and procedure, and there were no signs of proarrhythmia despite marked delay in ventricular repolarization in some individuals. Conclusions: AZD1305 shows electrophysiological characteristics indicative of potential antiarrhythmic efficacy in atrial fibrillation.
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| 37. |
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| 38. |
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| 39. |
- Wiklund, Annaeva, et al.
(författare)
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Levosimendan attenuates hypoxia-induced pulmonary hypertension in a porcine model.
- 2012
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 59:5, s. 441-449
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Levosimendan was hypothesized to attenuate hypoxic pulmonary vasoconstriction (HPV). METHODS: 14 anaesthetized pigs (30,9±1,0kg) were studied in normoxia (FiO2∼0,21) and hypoxia (FiO2∼0,10), before and 10-90 min after infusion of placebo (n=7) or Levosimendan (n=7). RESULTS: Compared to normoxia, hypoxia-baseline at FiO2∼0,10 (n=14) increased PVR by 1.9±0.4 WU (p<0,001), MPAP by 14.3±0.9 mmHg (p<0,001), MRAP by 2.1±0.4 mmHg (p<0,001), PCWP by 1.5±0.3 mmHg (p<0,001), CO by 1.3±0.2 L·min (p<0,001) and HR by 19.9±5.5 beats·min (p<0,001). SVR decreased by 7,2±1.0 WU (p<0,001), MAP and SV remained unaltered (p=ns). Compared to hypoxia-baseline, Levosimendan decreased MPAP and PVR (p<0,05), by ∼9 and ∼19%, respectively, plateauing between 10-90 min. SV increased (p<0,05) by ∼22%, plateauing after 60 min. MRAP, PCWP, HR, CO, MAP, SVR and blood-O2-consumption remained unaltered (p=ns). Compared to hypoxia-baseline, with placebo, MPAP remained stable (p=ns), PVR increased (p<0,05) and CO decreased (p<0,05), by ∼20 and ∼11% after 60-90 and 30-90min, respectively. SV decreased (p<0,05) by ∼8%, plateauing after 60-90min. PCWP and MRAP decreased (p<0,05) by ∼12%, plateauing after 10-60 and 10-90min, respectively. MPAP, HR, MAP, SVR and blood-O2-consumption remained unchanged (p=ns), except at 60min where MAP decreased (p<0,05) by ∼4%. CONCLUSIONS: Levosimendan attenuated HPV and the cardio-depressive effect of sustained hypoxia.
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| 40. |
- Johanson, Aki, et al.
(författare)
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Long-term follow-up in depressed patients treated with ECT
- 2005
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Ingår i: Journal of ECT. - 1533-4112. ; 21:4, s. 214-220
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Tidskriftsartikel (refereegranskat)abstract
- Design: The aim was to study the long-term effects of electroconvulsive therapy (ECT) in depression. 55 patients were followed-up 20-24 years after an ECT series. 13 patients were still alive and 10 agreed to participate in the study. All 55 patients had been investigated with clinical and neuropsychological assessment and with neurophysiological measurements; regional Cerebral Blood Flow (rCBF) and EEG before the first ECT, six months later and after about one year. These investigations were now repeated in the 10 patients. Results: Before the original ECT series all patients had suffered from severe mood disorder. At the follow-up the 10 patients showed no clear signs of mood disorder or cognitive impairment. There was a slightly subnormal performance in working memory and in verbal as well as visual episodic memory on all three occasions after the ECT series. The rCBF measurement showed a significant average CBF decrease from the first to the last measurement. There was, moreover, a significant rCBF decrease in frontal areas at the last measurement compared to the three previous assessments. Conclusion: All ten patients followed-up 20 – 24 years after an ECT series were mentally healthy and thus besides a moderate visual memory dysfunction no severe side effects were observed with clinical and neuroimaging techniques.
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