Comparative hemodynamic studies of isradipine and dihydralazine in atherosclerotic and normal rabbits.
The hemodynamic effects of the calcium antagonist isradipine (code name PN 200-110) and the arteriolar vasodilator dihydralazine were compared in atherosclerotic (cholesterol-fed) and normal conscious rabbits with implanted catheters. Regional blood flows were measured using the microsphere technique. Cardiac output and blood flow to several organs, especially to the gastrointestinal system, but not to the heart and brain, were lower in atherosclerotic rabbits than in normal ones. Intravenous isradipine (10 and 30 micrograms/kg) increased heart rate less in atherosclerotic than in normal rabbits. Isradipine had no effect on the surface electrocardiogram (ECG). In contrast, 0.4 mg/kg dihydralazine caused depression of the ST segment while decreasing blood pressure similarly. This was explained partly by an intramyocardial maldistribution of coronary blood flow (using microspheres). Isradipine increased and dihydralazine decreased flow to the brain. Isradipine redistributed cardiac output in atherosclerotic and normal animals in favor of the heart, brain, and skeletal muscle. However, in atherosclerotic animals, the high dose was less effective than the low dose in some vascular beds. Thus, isradipine is not a general vasodilator in either atherosclerotic or in normal animals, but favors the vital organs. This redistribution of cardiac output contrasts favorably with that induced by dihydralazine.
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Cardiovascular Unit of Preclinical Research, Sandoz Ltd., Basel, Switzerland.
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Takiguchi
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D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000503:physiopathology; D004078:Dihydralazine / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006830:Hydralazine / Q000031:analogs & derivatives*; D017275:Isradipine; D008863:Microspheres; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects
D002121:Calcium Channel Blockers; D011725:Pyridines; D006830:Hydralazine; D004078:Dihydralazine; D017275:Isradipine