PHARMACOLOGICAL MODIFICATION OF THE EDEMA PRODUCED BY COMBINED INFUSIONS OF PROSTAGLANDIN-E1 AND BRADYKININ IN CANINE FORELIMBS

Abstract

In dogs anesthetized with pentobarbital, 60 min local intraarterial infusions of prostaglandin E1 (4 .mu.g/min) together with bradykinin (10 .mu.g base/min) into forelimbs perfused at a constant pump controlled flow rate produced decreases in perfusion pressure and very marked increases in lymph flow, lymph total protein concentration, total protein transport and weight (266 g). Pretreatment with indomethacin did not reduce the marked increases in these parameters produced by the combined prostaglandin E1-bradykinin infusions. Treatment with diphenhydramine completely prevented the increases in lymph flow, lymph total protein concentration, total protein transport, weight and vasodilation produced by infusions of histamine, but not those produced by infusions of prostaglandin E1 or bradykinin. Pretreatment with methylprednisolone prevented the increases in lymph flow, lymph total protein concentration, total protein transport, weight and vasodilation produced by infusions of histamine, but not those produced by infusions of prostaglandin E1 or bradykinin. Pretreatment with methylprednisolone prevented the increases in lymph flow, lymph total protein concentration, total protein transport and weight produced by infusions of prostaglandin E1, but not those produced by combined infusions of high doses of histamine or bradykinin. Treatment with either methylprednisolone or diphenhydramine reduced the marked increases in these parameters produced by combined infusions of prostaglandins E1 and bradykinin to levels produced by infusions of prostaglandin E1 and bradykinin to levels produced by infusions of bradykinin alone. Vasopressin or isoproterenol treatment essentially prevented the marked increases in lymph flow, lymph total protein concentration, total protein transport and weight produced by combined infusions of prostaglandin E1 and bradykinin. The potentiation of the bradykinin edema formation produced by prostaglandin E1 apparently results from an endogenous release of histamine and treatment with vasopressin or isoproterenol essentially prevents the development of edema produced by combined infusions of these autoacids. The potentiation is not dependent on the vasodilator action of prostaglandin E1 as it may be demonstrated under constant controlled flow conditions.