Mechanism of the hypotensive effect of prazosin

Prazosin is a quinazoline that has a long lasting hypotensive effect. To investigate the mechanisms underlying its action experiments were performed in 75 dogs anesthetized with pentobarbitone sodium. Prazosin, after i.v. injection, lowered arterial pressure without altering heart rate and venous pressure, and decreased pressor responses to epinephrine, norepinephrine and splanchnic nerve stimulation. Orthocarboxybenzeno-seleninic acid, an alpha-adrenoceptor blocker, antagonized the hypotensive effect of prazosin. Neither administration of propranolol nor carotid sinus local anesthesia impaired prazosin hypotensive effects. Topical application of prazosin on both carotid sinuses had no effect on general arterial blood pressure; after intravenous administration it did not change the hypotension caused by electrical stimulation of the carotid sinuses. The depressor effects of papaverine and sodium nitrite on blood pressure were enhanced by prazosin. It is concluded that this drug exerts its hypotensive effect by blocking, alpha-adrenoceptors and by possibly relaxing vascular smooth muscle.