Effect of calcium antagonist darodipine on the isolated human heart.
Darodipine is a new light stable dihydropyridine calcium antagonist. In isolated large conductance vessels from experimental animals, darodipine blocks the potential-dependent but not the receptor-operated calcium channel. We studied the effects of darodipine in isolated human epicardial coronary arteries and in isolated right ventricular trabecula obtained from the explanted hearts of patients undergoing cardiac transplantation. In the coronary artery, the PD'2 for calcium was 9.7 and for carbachol was 9.5. In the cardiac muscle, the PD'2 for calcium was 6.5. Using 45Ca2+, darodipine blocked uptake in presence of potassium and histamine. We conclude that darodipine is (1) a potent calcium antagonist in the isolated human coronary artery, but not in ventricular myocardium, thus showing very pronounced target tissue selectivity, and (2) in contrast to findings obtained in rabbit aorta, it inhibits contraction and 45Ca2+ uptake mediated by both the potential-dependent and receptor-operated channels in the human epicardial coronary artery.
D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011189:Potassium Chloride; D006632:Histamine; D002217:Carbachol; D009543:Nifedipine; C034600:darodipine; D002118:Calcium