Coronary and Systemic Hemodynamic Effects of Dihydropyridines

Abstract

The slow channel calcium blocking agents are a structurally diverse group of compounds which share a common property of interfering with excitation-contraction coupling in myocardium and vascular smooth muscle. Because these drugs have varying structures, their hemodynamic properties have been found to produce different cardiovascular actions. This is best documented for nifedipine, diltiazem and verapamil [1,2]. Dihydropyridines form a subgroup within the general category of calcium antagonists. Many compounds with the basic dihydropyridine nucleus have been synthesized and whereas certain of these agents have been shown to possess calcium channel blocking activity in vitro and in vivo, more recently, others have been found to posses calcium agonist activity [3, 4]. The present investigation was undertaken to compare varying compounds with the dihydropyridine nucleus as to their systemic and coronary hemodynamic actions. The calcium antagonists, nifedipine, nisoldipine, nitrendipine, niludipine and FR 34235 and the calcium agonists, CGP 28392 and Bay k 8644 were studied in various doses. Because much of the previous work with these agents had been completed in anesthetized animals or in vitro, conscious dogs were used to avoid potential interactions with anesthetics and to maintain cardiovascular reflexes intact.