HEMODYNAMIC EFFECTS OF PRAZOSIN

Abstract

Prazosin, 0.001-10 mg/kg, was administered i.v. to anesthetized normal rats. In the dose range 0.001-0.01 mg/kg, the drug induced highly significant, dose-related falls in blood pressure, pulse pressure and heart rate. With doses above 0.01 mg/kg, there was a plateau in hypotensive efficacy and a diminution in negative chronotropic activity. Both actions of prazosin (0.01 mg/kg) were unaffected by vagal blockade with atropine, while hypotensive potency was unimpaired after .beta.-adrenoreceptor blockade. The vasodilator, diazoxide, lowered blood pressure, widened pulse pressure and caused tachycardia in rats pre-treated with pentolinium. All effects of prazosin were abolished by ganglion blockade. These findings, together with the absence of compensatory tachycardia or gross renin hypersecretion during prazosin-induced hypotension, are compatible with an antisympathotonic mode of action for the drug. Consistent with its effects on cyclic nucleotide distribution, prazosin appears to enhance isoprenaline-induced .beta.-receptor stimulation.