The hemodynamics of calcium-channel antagonists in hypertension: vascular and myocardial responses.
Hemodynamic studies have indicated that the mechanism of the antihypertensive effect of calcium-channel antagonists is reduction of systemic vascular resistance. However, potential negative inotropic effects could have an adverse effect on myocardial performance. In this study, we evaluated the hemodynamic response to the prototypic calcium-channel antagonist, verapamil, in patients with moderate-to-severe hypertension. We gave incremental infusions of verapamil in subsystemic doses into the brachial artery of an isolated forearm preparation. The response to 10 micrograms/min/100 ml revealed a reduction in forearm vascular resistance from 55 to 21 units and an increase in forearm blood flow from 3.57 to 7.54 ml/min/100 ml (both p less than .01). Intravenous administration of verapamil as a bolus (0.15 mg/kg) and continuous infusion (1 or 2 mg/min) resulted in a significant decrease in mean arterial pressure and systemic vascular resistance as well as a significant increase in cardiac index and stroke volume index. This occurred without a significant increase in pulmonary wedge pressure. One week of oral therapy resulted in a significant reduction of mean arterial pressure and systemic vascular resistance both at rest and at peak exercise, associated with a significant increase in stroke volume index and no increase in pulmonary wedge pressure. These findings document the direct vasodilator effects of the prototypic calcium-channel antagonist verapamil in patients with moderate-to-severe hypertension. In addition, these data show that myocardial performance can improve during therapy, when myocardial reserve is sufficient, and the adverse effects of systemic vasoconstriction are reversed by therapy.
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002319:Cardiovascular System / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009129:Muscle Tonus / Q000187:drug effects; D014700:Verapamil / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D014700:Verapamil