Calcium channel blockers and asthma

The activation of rabbit aortic smooth muscle was studied by two most widely used vascular smooth muscle stimulants: alpha-adrenoceptor activation by norepinephrine (NE) and high-K+ depolarization. This was studied by measurements of isometric contractions and net as well as unidirectional Ca2+ fluxes. These parameters showed markedly differential sensitivities towards tow smooth muscle inhibitors used in this study: D600 and amrinone. By choosing an appropriate concentration of D600 or amrinone, Ca2+ uptake or Ca2+ influx induced by high K+ or NE could by selectively inhibited. Furthermore, by using unidirectional flux measurements it was demonstrated that Ca2+ influx stimulated by NE and high K+ were additive in nature. The data from the addivity experiment exclude the interpretation of a common Ca2+ pathway with two separate mechanisms for opening it. The data on three criteria employed in this study provide evidence for the existence of two independent Ca2+ pathways, one for each mode of activation, for Ca2+ influx known to be associated with these contractions.

Calcium ions play an important role in the cardiovascular system. They are involved in electrophysiologic processes, link excitation to muscular contraction, control energy storage and utilization, and constrict vascular smooth muscle in coronary and systemic arteries. A new group of pharmacologic agents that block the passage of calcium ions across cell membranes has been developed. These agents act during the slow inward current of cellular depolarization. The most extensive clinical experience has been obtained with four of these agents: verapamil, nifedipine, perhexiline, and diltiazem. Verapamil, which has profound electrophysiologic effects on the slow inward current, is emerging as a valuable antiarrhythmic agent. Re-entrant supraventricular arrhythmias, such as paroxysmal supraventricular tachycardia, are particularly amenable to treatment with intravenous verapamil. Preliminary trials of long-term therapy with oral verapamil for control of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia suggest that this agent is effective for therapy of these arrhythmias.