Gastric vascular actions of prostanoids and the dual effect of arachidonic acid

Abstract

The effects of several prostanoids and arachidonic acid on gastric vascular perfusion pressure were studied in dogs. A chambered segment of gastric fundus in anesthetized, heparin-treated dogs was perfused at constant flow (10 ml .cntdot. min-1) with femoral arterial blood. Changes in perfusion pressure were measured after intra-arterial injection of each agent, at a point from which it reached the stomach in 3 s. Prostacyclin, prostaglandin [PG]E2 and PGE1 (5-40 ng) reduced perfusion pressure by 10-35 mm Hg and were equipotent. 6-oxo-PGE1, the endoperoxide PGH2, and 2 stable prostacyclin analogs carbacyclin and 6.beta.-PGI1 were less potent vasodilators; 6-oxo-PGF1.alpha. was inactive. The epoxymethano endoperoxide analogs (U-46619 and U-44069) were equipotent vasoconstrictors, doses of 10-100 ng causing increases in perfusion pressure of 10-35 mm Hg. PGF2.alpha. and noradrenaline [norepinephrine] also had vasoconstrictor actions. PGDw had inconsistent actions. The effect of arachidonic acid on perfusion pressure varied with the length of time in contact with blood. Close (3 s incubation) intra-arterial injection (25-200 .mu.g) produced vasodilation; distal intra-arterial injection, which allowed 30 s of contact with blood before reaching the stomach, produced vasoconstriction as evidenced by dose-related increases in perfusion pressure (10-65 mm Hg). Arachidonic acid, given by close intraarterial injection, is converted to the stomach mainly to vasodilator substances, presumably PGI2 or PGE2, but is converted mainly to a vasoconstrictor substance, presumably thromboxane A2, when allowed to mix with blood for 30 s.