| 1. |
- 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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| 2. |
- Fu, Michael, 1963, et al.
(författare)
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Decreased density of mesenteric arteries but not of myocardial endothelin receptors and function in rats with chronic ischemic heart failure.
- 1993
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 22:2, s. 177-82
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Tidskriftsartikel (refereegranskat)abstract
- Mesenteric artery and cardiac ventricular endothelin receptors and endothelin-1-induced pressor responses were studied in normal rats and rats with chronic congestive heart failure induced by myocardial ischemia (4 weeks after coronary artery ligation). In mesenteric arteries of rats with chronic ischemic heart failure, endothelin receptor density was significantly decreased by 59%, whereas the dissociation constant was increased 2.8-fold, as compared with controls. There were, however, no changes in endothelin-receptor density or the dissociation constant in cardiac ventricular membrane preparations from rats with congestive heart failure as compared with controls. In pithed rats with congestive heart failure there was a reduced pressor response to a bolus injection of endothelin-1 (800 pmole/kg body weight), while the vasodilatory response was unaltered as compared with sham-operated controls. These results demonstrate that there is a decreased vascular endothelin-receptor function due to a down-regulated endothelin receptor. The in vivo data indicate that this is due to impaired endothelin A but not endothelin B receptor function. Thus, there is an impaired arterial but not cardiac ventricular endothelin receptor-mediated signalling system in the rat with chronic ischemic heart failure.
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| 3. |
- 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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| 4. |
- Jern, Sverker, 1954, et al.
(författare)
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Swedish Isradipine Study in Hypertension: evaluation of quality of life, safety, and efficacy. SWISH Group.
- 1991
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 18 Suppl 3
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Tidskriftsartikel (refereegranskat)abstract
- This was a double-blind multicenter study to compare the efficacy, tolerability and effects on the quality of life with isradipine and atenolol in the treatment of essential hypertension. Of 588 patients entering the 6-week placebo run-in period, 549 were eligible for randomization to receive either isradipine or atenolol for 8 weeks. If, at the end of this period, diastolic blood pressure (DBP) remained greater than 90 mm Hg, then both agents were given in combination for a further 10 weeks. Tolerability and quality of life were assessed repeatedly during the placebo and active-treatment phases. A subgroup of 30 patients were followed by 24-h ambulatory blood pressure monitoring, and their results are now being analyzed. In another subgroup of 26 patients, maximum exercise capacity, as determined by ergometer bicycle-testing, was measured once during placebo and twice during active treatment. At the end of the 24-week study period, both isradipine and atenolol as monotherapy had produced significant decreases in blood pressure. There were no significant differences overall between the compounds in quality-of-life and side-effect profiles, although there was a relative absence of ankle edema and headache with isradipine. Furthermore, patients receiving isradipine had no change in performance on exercise testing whereas patients on atenolol had a significant decrease (p less than 0.01).
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| 5. |
- Olsson, Bertil, et al.
(författare)
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Effect of pentisomide (CM 7857) on myocardial excitation, conduction, repolarization, and refractoriness. An electrophysiological study in humans
- 1991
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Ingår i: Journal of Cardiovascular Pharmacology. - 0160-2446. ; 18:6, s. 54-849
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Tidskriftsartikel (refereegranskat)abstract
- The electrophysiological effects of pentisomide upon the intact human heart were evaluated using programmed stimulation and recording of intracardiac monophasic action potentials (MAP) in 17 patients with various ventricular arrhythmias. After i.v. administration of pentisomide, 85-135 mg, the atrial-His interval increased by 8 +/- 12 ms (p less than 0.05) during sinus rhythm and by 13 +/- 21 ms (p less than 0.05) at atrial pacing of 600 ms cycle length (600 ms pacing). The His-ventricular interval also increased by 6 +/- 10 ms during sinus rhythm (p less than 0.05) and by 5 +/- 9 ms at 600 ms pacing (NS). The QRS duration prolonged by 9 +/- 10 ms (p less than 0.01) and 6 +/- 8 ms (p less than 0.01) during 600 and 500 ms ventricular pacing, respectively. The right ventricular MAP duration to 90% repolarization was significantly shortened, by 20 +/- 21 ms (p less than 0.01) during sinus rhythm, by 16 +/- 17 ms (p less than 0.01) at 600 ms ventricular pacing, and by 11 +/- 16 ms (p less than 0.01) at 500 ms ventricular pacing. The corrected QT interval was shortened by 21 +/- 28 ms (p less than 0.01). The present study supports that pentisomide is a class-I antiarrhythmic agent with a marked effect on depolarization (action of class Ia and Ic) and on repolarization (action of class Ib). This unique combination of cellular electrophysiological properties indicates that the clinical antiarrhythmic efficacy of pentisomide may differ from that of hitherto available antiarrhythmic drugs.
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