Analysis of responses to bradykinin in the rat hindquarters vascular bed. Nossaman, Bobby Dean, Alan David Kaye, Chang Jian Feng, Bin Kang, and Philip J. Kadowitz. Departments of Anesthesiology and Pharmacology, Tulane University Medical School, New Orleans, La 70112-2699
APStracts 3:0342R, 1996.
The mechanism by which bradykinin (BK) decreases vascular resistance was investigated in the hindquarters vascular bed of the rat. Under conditions of controlled blood flow, BK produced dose related decreases in hindquarters perfusion pressure when injected into the perfusion circuit in doses of 0.1-1.0?[mu]g. Responses to BK were reproducible with respect to time and HOE?140 (d-Arg-[Hyp3, Thi5, d -Tic7, Oic8]?BK), a kinin B2 receptor antagonist, decreased hindquarters vasodilator responses to the peptide. HOE?140 had no significant effect on responses to vasodilator agents which act by a variety of pharmacologically distinct mechanisms. Nitric oxide synthase inhibitors, Nw-nitro-l-arginine methyl ester or Nw-nitro-l -arginine benzyl ester, did not decrease responses to BK in doses that decreased hindquarters vasodilator responses to acetylcholine. The cyclooxygenase inhibitors, meclofenamate and indomethacin, had no effect on responses to BK in doses that attenuated vasodilator responses to the prostaglandin precursor, arachidonic acid. Clotrimazole or ETYA (5, 8, 11, 14-eicosatetraynoic acid), cytochrome P450 arachidonic acid metabolism inhibitors, in doses that attenuated vasodilator responses to arachidonic acid, had no effect on responses to BK. Glybenclamide or U37883A (4-morpholinecarboximidine-N-1 -adamantyl-N'-cyclohexyl), K+ATP channel antagonists, in doses that attenuated responses to lemakalim, had no significant effect on responses to BK. Finally, des-Arg9BK, a reported kinin B1 receptor agonist, decreased hindquarters perfusion pressure when injected in doses of 3-30?[mu]g and responses to the B1 agonist were attenuated by HOE?140. The observation that des-Arg9BK, in high doses, induces modest HOE?140 sensitive responses suggest that kinin B1 receptors are not normally expressed in the hindquarters vascular bed of the rat. The present results indicate that BK dilates the hindquarters vascular bed by a kinin B2 receptor mechanism that is independent of the release of nitric oxide, cyclooxygenase or P450 metabolites of arachidonic acid or the activation of K+ATP channels. 

Received 2 May 1996; accepted in final form 26 August 1996.
APS Manuscript Number R246-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996