[Mechanism of the hypotensive effect of prostaglandins A2 and E2]

In anesthetized dogs the intravenous injection of prostaglandins (PGs) A2 and E2 (5-200 micrograms/kg) produced a dose-dependent fall (P less than 0.001) of the blood pressure with blockade of the baroreceptor reflex. The hypotension can increase the heart rate and decrease myocardial contractile force, which is neither prevented by atropine, phentolamine, diphenhydramine, verapamil nor by inhibitors of prostaglandin synthesis. Intravenous, intraaortic or intraventricular (left) injections evoked an equipotent fall of the arterial pressure. Less decrement is elicited by the intramuscular injection. The gastric route is ineffective. The intracisternal injection of high doses (20-130 micrograms/kg) of prostaglandins A2 or E2 decreases the blood pressure slightly after 5-10 minutes, probably because of prostaglandins transport across the blood-brain barrier. The blood pressure increases by stimulation of the sympathetic nerves of the spleen and of the liver, or by exogenous noradrenaline are equally significative before and after the injections of prostaglandins A2 or E2. Indomethacin and aspirin failed to affect the pressor increase produced by stimulation of the sympathetic nerves, or that of the exogenous noradrenaline in the normal dogs or in animals injected previously with PGs. It is concluded that the hypotensive action of the PGs is due to peripheric vasodilatation apparently without inactivation by the lung.