The Actions of Nifedipine and Nisoldipine on the Contractile Activity of Human Coronary Arteries and Human Cardiac Tissue in Vitro

Abstract

We have studied the action of nifedipine and nisoldipine on the contractile activity of human isolated coronary arteries and human isolated auricular and ventricular muscles. Nisoldipine depressed dose dependently the spontaneous rhythmic contractions displayed by the coronary artery preparations and at 1 nM abolished these contractions. Nisoldipine was twenty times more potent than nifedipine as an inhibitor of increase in tone induced by depolarization (100 mM K+). The rhythmic activity induced by serotonin (10 microM) was about five times more sensitive to nisoldipine than to nifedipine. In both auricular and ventricular preparations, isoprenaline evoked an increase in the rate of force development and in the rate of relaxation. Nifedipine was five times (ventricular muscles) and ten times (auricular muscles) more potent than nisoldipine as a negative inotropic agent. The present observations in human isolated preparations indicate that nisoldipine shows a higher vascular selectivity than nifedipine.

SUT-8701, a Cholecystokinin Analog, Prevents the Cholinergic Degeneration in the Rat Cerebral Cortex Following Basal Forebrain Lesioning

“…This property was observed in experiments on human tissues as well as animal ones (3). The coronary artery selectivity of nisol dipine was at least 10 times more pronounced than that of nifedipine (3), and the cardiodepressant effect was less po tent in human tissues (3). From such a pharmacological point of view, nisoldipine seems to be a promising drug for the treatment of ischemic heart disease.…”

Nisoldipine CC: Efficacy and tolerability in hypertension and ischemic heart disease

“…In this respect, nisotdipine is 100 times more vascular selective than nifedipine and is the most vascular selective of the currently available CCBs [11]. Nisoldipine, therefore, has the capacity to lower blood pressure without affecting the functioning of either the myocardium or skeletal muscle and does not produce the negative inotropic effects that occur with some other CCBs, such as nifedipine [12,13]. There is some evidence from in vitro studies, particularly using porcine artery preparations, that nisoldipine preferentially acts on the coronary rather than the peripheral vasculature, especially when the former is in a depolarized state, such as occurs during periods of ischemia [12,14,15].…”

“…Nisoldipine, therefore, has the capacity to lower blood pressure without affecting the functioning of either the myocardium or skeletal muscle and does not produce the negative inotropic effects that occur with some other CCBs, such as nifedipine [12,13]. There is some evidence from in vitro studies, particularly using porcine artery preparations, that nisoldipine preferentially acts on the coronary rather than the peripheral vasculature, especially when the former is in a depolarized state, such as occurs during periods of ischemia [12,14,15]. However, the results of clinical studies have not supported these observations but have suggested, instead, that nisoldipine acts equally on coronary and peripheral arteries [16][17][18].…”

Vasodilatory effects of nisoldipine on coronary arteries—Correlation with plasma levels

“…Nisoldipine is a new dihydropyridine calcium antagonist with high vascular specificity [1,2]; systemic and coronary vascular resistance are substantially attenuated by nisoldipine, whereas myocardial contractility seems to be virtually unaffected by vasoactive doses of the drug [3][4][5]. However, the effects of nisoldipine on myocardial contractility in isolated systems are controversial [6].…”