Inhibition of bradykinin- and kallikrein-induced cerebral arteriolar dilation by a specific bradykinin antagonist.
We have previously shown that topical brain application of kallikrein, an enzyme which converts kininogen to bradykinin, induces rabbit pial arteriole dilation. The purpose of the present investigation was to utilize a newly developed competitive kinin receptor antagonist to test the hypothesis that kallikrein-induced dilation was due to the conversion of brain kininogen to vasoactive kinins. As in our previous study, we measured rabbit pial arteriole diameter with a microscope using the closed cranial window technique. The kinin antagonist (6 microM) reduced the dose-dependent dilation produced by bradykinin and blocked the dilation induced by kallikrein. In addition, the kinin antagonist was specific since it did not alter the cerebral arteriole dilation produced by adenosine, acetylcholine, or vasoactive intestinal polypeptide. These experiments provide further evidence for a possible role of the endogenous brain kallikrein-kinin system in the modulation of the cerebral circulation and provide the necessary pharmacologic foundation for future use of this antagonist in testing the role of kinins in the normal or altered cerebral circulation.
D000595:Amino Acid Sequence; D000818:Animals; D001160:Arterioles; D001794:Blood Pressure; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D007610:Kallikreins; D001920:Bradykinin