des-Arg9-bradykinin produces tone-dependent kinin B1 receptor-mediated responses in the pulmonary vascular bed.
Responses to des-Arg9-bradykinin, a selective kinin B1 receptor agonist, were characterized in the pulmonary vascular bed of the intact-chest cat. Injections of des-Arg9-bradykinin into the perfused lobar artery under low-resting tone conditions caused dose-related increases in lobar arterial pressure; whereas in the same experiment under elevated tone conditions, injections of the B1 agonist caused dose-related decreases in lobar arterial pressure. Vasoconstrictor responses to des-Arg9-bradykinin under low-tone conditions and vasodilator responses under elevated-tone conditions were antagonized by des-Arg9,[Leu8]-bradykinin, a kinin B1 receptor antagonist, whereas responses under low- and high-tone conditions were not altered by Hoe 140, a kinin B2 receptor antagonist. Vasoconstrictor responses to des-Arg9-bradykinin under low-tone conditions were attenuated by phentolamine, prazosin, and reserpine but not by sodium meclofenamate, suggesting that release of catecholamines and activation of alpha-adrenergic receptors are involved. Pulmonary vasodilator responses under elevated-tone conditions were inhibited by N omega-nitro-L-arginine methyl ester, suggesting that des-Arg9-bradykinin stimulates the release of nitric oxide, whereas meclofenamate and U-37883A, a nonsulfonylurea ATP-sensitive K+ channel antagonist, did not alter vasodilator responses to the B1 receptor agonist. These results suggest that vasoconstrictor responses to des-Arg9-bradykinin under low-tone conditions are mediated by the activation of kinin B1 receptors, the release of catecholamines within the lung, and the activation of alpha-adrenergic receptors, whereas vasodilator responses under elevated tone conditions are mediated by activation of B1 receptors and the release of nitric oxide from the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
DeWitt
B J
BJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Cheng
D Y
DY
Kadowitz
P J
PJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002415:Cats; D005260:Female; D008168:Lung / Q000098:blood supply* / Q000502:physiology*; D008297:Male; D011652:Pulmonary Circulation; D018002:Receptors, Bradykinin / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C065679:icatibant; D001920:Bradykinin