Pharmacological modification of the edema produced by combined infusions of prostaglandin E1 and bradykinin in canine forelimbs.
In dogs anesthetized with pentobarbital, 60 min local i.a. infusions of prostaglandin E1 (4 micrograms/min) together with bradykinin (10 micrograms 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 significantly reduce the very 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 and weight produced by infusions of prostaglandin E1, but not those produced by infusions of high doses of histamine or bradykinin. Treatment with either methylprednisolone or diphenhydramine significantly reduced the very marked increases in these parameters produced by combined infusions of prostaglandin E1 and bradykinin to levels produced by infusions of bradykinin alone. Vasopressin or isoproterenol treatment essentially prevented the very marked increases in lymph flow, lymph total protein concentration, total protein transport and weight produced by combined infusions of prostaglandin E1 and bradykinin. These data suggest that the potentiation of the bradykinin edema formation produced by prostaglandin E1 results from an endogenous release of histamine and that treatment with vasopressin or isoproterenol essentially prevents the development of edema produced by combined infusions of these autacoids. Moreover, the potentiation is not dependent on the vasodilator action of prostaglandin E1 as it may be demonstrated under constant controlled flow conditions.
D000527:Alprostadil; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D004155:Diphenhydramine / Q000494:pharmacology; D004285:Dogs; D004357:Drug Synergism; D004487:Edema / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D005552:Forelimb / Q000098:blood supply; D006636:Histamine Release / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology
D011458:Prostaglandins E; D014667:Vasopressins; D004155:Diphenhydramine; D000527:Alprostadil; D007545:Isoproterenol; D001920:Bradykinin; D008775:Methylprednisolone; D007213:Indomethacin