MECHANISM OF THE VASOCONSTRICTOR ACTION OF PROSTAGLANDIN B

¹ Departments of Internal Medicine (Division of Clinical Pharmacology) and Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa

The mechanism of PGB-induced vasoconstriction was studied in the dog hindpaw perfused at constant flow. Intra-arterial infusions of PGB₂ (50-800 ng/kg/min) and PGB₁ (200-3200 ng/kg/min) produced vasoconstriction. Depletion of catecholamines by reserpine (0.5 mg/kg/day for 2 days) decreased PGB-induced vasoconstriction. PGB₂ (50-200 ng/kg/min) was a vasodilator in reserpine-pretreated animals. A tropine (300 µg/kg) and decamethonium (2 mg/kg) did not affect PGB-induced vasoconstriction. Cocaine (2 µm/kg/min) enhanced PGB₁-and PGB₂-induced vasoconstriction, whereas blockade of sodium conductance and neuronal depolarization with tetrodotoxin (200 ng/kg/min) reduced vasoconstrictor responses to PGB₁ and PGB₂. Infusions of l-norepinephrine in reserpine-pretreated animals restored the responses to intra-arterial tyramine but not those to sympathetic nerve stimulation, PGB₁ and PGB₂. Since cate-cholamine depletion and blockade of depolarization reduced pressor responses to PGB compounds and since repletion of cytoplasmic norepinephrine stores did not restore PGB-induced vasoconstriction, the data show that PGB compounds release norepinephrine from the granular store by a mechanism dependent on depolarization.