Acute hemodynamic effects of pinacidil and hydralazine in essential hypertension

In a double-blind, randomized, crossover study, the effects of intravenous pinacidil, 0.2 mg/kg, were compared with those of hydralazine, 0.3 mg/kg, before and after beta-adrenoceptor blockade in six subjects with hypertension. Both drugs equally reduced total peripheral resistance by about 40%. Pinacidil reduced mean blood pressure by an average of 30 mm Hg, while the reduction after hydralazine was 10 mm Hg. The difference in antihypertensive effect resulted from greater increases in heart rate, cardiac contractility (systolic time intervals), and cardiac index (thermodilution) after hydralazine. These effects after hydralazine could not be fully abolished by beta-blockade, as could the effects after pinacidil. Pinacidil decreased pulmonary blood pressure, whereas there was a slight rise in pulmonary blood pressure after hydralazine. Forearm blood flow (venous occlusion strain gauge plethysmography) increased equally after both drugs; thus pinacidil decreased forearm vascular resistance more than hydralazine did. Serum concentrations of both drugs were within the therapeutic range and correlated with the fall in mean blood pressure. Five subjects complained of side effects after hydralazine, but none were reported after pinacidil. Hydralazine increased myocardial oxygen consumption (as estimated from the rate-pressure product) by 35%; there was no change after pinacidil. It is suggested that hydralazine has direct cardiostimulatory effects that limit its antihypertensive effectiveness. These effects increase myocardial oxygen consumption and may be responsible for the common and sometimes severe cardiovascular side effects of hydralazine.