Prostaglandin and histamine involvement in the gastric vasodilator action of pentagastrin.

Male mongrel dogs were anesthetized with 30 mg/kg of pentobarbital and left gastric arterial blood flow (GBF) was measured with electromagnetic flow probes. Pentagastrin, 1microng/kg i.v., produced an initial brief increase in flow followed by a prolonged secondary increase. Histamine, 1 microng/kg, and prostaglandin E2, 0.5 microng/kg, produced monophasic short-lived increases in GBF. The histamine H1 antagonist diphenhydramine and the H2 antagonist metiamide did not affect resting GBF. The prostaglandin synthesis inhibitor, indomethacin, reduced resting GBF by 46%. Responses to histamine were blocked by diphenhydramine by 81% and reduced by indomethacin by 21%. Responses to prostaglandin E2 were reduced by indomethacin by 21%. The primary pentagastrin response was blocked by diphenhydramine by 54%. The secondary pentagastrin response was blocked by both metiamide by 69% and indomethacin by 71%. We conclude that GBF is maintained by a basal production of vasodilatory prostaglandins. Furthermore, pentagastrin can release histamine which by acting on H2 receptors can enhance the production and/or release of prostaglandins to finally mediate an increase in GBF. These actions may partly explain the deleterious effect of indomethacin and the curative effect of prostaglandins on gastric mucosal ulcers.