| 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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| 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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