Relaxation to bradykinin in bovine pulmonary supernumerary arteries can be mediated by both a nitric oxide-dependent and -independent mechanism

1 The aim of the present study was to determine the relative contribution of prostanoids, nitric oxide and K+ channels in the bradykinin-induced relaxation of bovine pulmonary supernumerary arteries. 2 In endothelium-intact, but not denuded rings, bradykinin produced a concentration-dependent relaxation (pEC(50), 9.6+/-0.1), which was unaffected by the cyclo-oxygenase inhibitor indomethacin. The nitric oxide scavenger hydroxocobalamin (200 muM, pEC(50), 8.5+/-0.2) and the nitric oxide synthase inhibitor L-NAME (100 muM, pEC(50), 8.9+/-0.1) and the combination Of L-NAME and hydroxocobalamin (pEC(50), 8.1+/-0.2) produced rightward shifts in the bradykinin concentration response curve. 3 The guanylyl cyclase inhibitor ODQ (10 muM, pEC(50), 9.6+/-.0.4) did not affect the response to bradykinin. 4 Elevating the extracellular [K+] to 30 mM did not affect the response to bradykinin but abolished the response when ODQ or L-NAME was present. 5 The K+ channel blocker apamin (100 nM), combined with charybdotoxin (100 nM), produced a small reduction in the maximum response to bradykinin but they abolished the response to bradykinin when ODQ, L-NAME or hydroxocobalamin were present. Apamin (100 nM) combined with iberiotoxin (100 nM) also reduced the response to bradykinin in the presence of hydroxocobalamin or L-NAME. 6 The concentration response curve for sodium nitroprusside-induced relaxation was abolished by ODQ (10 muM) and shifted to the right by apamin and charybdotoxin. 7 These studies suggest that in bovine pulmonary supernumerary arteries bradykinin can stimulate the formation of nitric oxide and activate an EDHF-like mechanism and that either of these pathways alone can mediate the bradykinin-induced relaxation. In addition nitric oxide, acting through guanylyl cyclase, can activate an apamin/charbydotoxin-sensitive K+ channel in this tissue.