DES-ARG(9)-BRADYKININ PRODUCES TONE-DEPENDENT KININ B1 RECEPTOR-MEDIATED RESPONSES IN THE PULMONARY VASCULAR FED

Responses to des-Arg(9)-bradykinin, a selective kinin B1 receptor agonist, were characterized in the pulmonary vascular bed of the intact-chest cat. Injections of des-Arg(9)-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-Arg(9)-bradykinin under low-tone conditions and vasodilator responses under elevated-tone conditions were antagonized by des-Arg(9),[Leu(8)]-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-Arg(9)-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-Arg(9)-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-Arg(9)-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. These data provide pharmacologic evidence for the existence of functionally active kinin B1 receptors that mediate tone-dependent vasoconstrictor and vasodilator responses in the pulmonary vascular bed of the cat.