ANALYSIS OF RESPONSES TO BRADYKININ - EFFECTS OF HOE-140 IN THE HINDQUARTERS VASCULAR BED OF THE CAT

The mechanisms and receptor subtype mediating vasodilator responses to bradykinin were investigated in the hindquarters vascular bed of the cat under constant flow conditions. Intraarterial injections of bradyk inin in doses of 10-1,000 ng into the hindquarters vascular bed caused dose-related decreases in perfusion pressure that were inhibited by H oe-140, a bradykinin Bz-receptor antagonist. Injections of des-Arg(9)- bradykinin (in doses 10-fold higher than for bradykinin) caused smalle r dose-related decreases in hindquarters perfusion pressure that were not blocked by Hoe-140. Administration of atropine, glibenclamide, or cyclooxygenase inhibitors did not alter vasodilator responses to brady kinin, suggesting that activation of muscarinic receptors, ATP-sensiti ve K+ channels, or prostaglandin release is not involved in the respon se to the peptide. Administration of N-omega-nitro-L-arginine and its methyl ester reduced vasodilator responses to bradykinin, acetylcholin e, and substance P, whereas responses to endothelium-independent vasod ilator agents were not attenuated. Decreases in systemic arterial pres sure and in hindquarters perfusion pressure in response to bradykinin were enhanced by the angiotensin-converting enzyme inhibitors captopri l and enalaprilat. These results suggest that hindquarters vasodilator responses to bradykinin are mediated by activation of kinin B-2 recep tors and in part by the release of nitric oxide. These data also sugge st the presence of bradykinin B-1 receptors, mediating vasodilation in the hindquarters vascular bed. These results indicate that bradykinin is rapidly inactivated by angiotensin-converting enzyme in the lung a nd in the hindquarters vascular bed of the cat.