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 bradykinin in doses of 10-1,000 ng into the hindquarters vascular bed caused dose-related decreases in perfusion pressure that were inhibited by Hoe-140, a bradykinin B2-receptor antagonist. Injections of des-Arg9-bradykinin (in doses 10-fold higher than for bradykinin) caused smaller 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 bradykinin, suggesting that activation of muscarinic receptors, ATP-sensitive K+ channels, or prostaglandin release is not involved in the response to the peptide. Administration of N omega-nitro-L-arginine and its methyl ester reduced vasodilator responses to bradykinin, acetylcholine, and substance P, whereas responses to endothelium-independent vasodilator agents were not attenuated. Decreases in systemic arterial pressure and in hindquarters perfusion pressure in response to bradykinin were enhanced by the angiotensin-converting enzyme inhibitors captopril and enalaprilat. These results suggest that hindquarters vasodilator responses to bradykinin are mediated by activation of kinin B2 receptors and in part by the release of nitric oxide. These data also suggest the presence of bradykinin B1 receptors, mediating vasodilation in the hindquarters vascular bed. These results indicate that bradykinin is rapidly inactivated by angiotensin-converting enzyme in the lung and in the hindquarters vascular bed of the cat.
Santiago
J A
JA
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Garrison
E A
EA
Kadowitz
P J
PJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D002415:Cats; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply*; D008297:Male
D016861:Cyclooxygenase Inhibitors; D001285:Atropine; C065679:icatibant; D002216:Captopril; D015773:Enalaprilat; D001920:Bradykinin; D005905:Glyburide