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Relaxation to bradykinin in bovine pulmonary supernumerary arteries can be mediated by both a nitric oxide‐dependent and ‐independent mechanism
Author(s) -
Tracey A,
Bunton D,
Irvine J,
MacDonald A,
Shaw A M
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704890
Subject(s) - bradykinin , apamin , charybdotoxin , hydroxocobalamin , chemistry , nitric oxide , medicine , iberiotoxin , endocrinology , sodium nitroprusside , endothelium derived hyperpolarizing factor , vasodilation , potassium channel , biochemistry , receptor , cyanocobalamin , vitamin b12
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. 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 μ M , pEC 50 , 8.5±0.2) and the nitric oxide synthase inhibitor L ‐NAME (100 μ M , 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. The guanylyl cyclase inhibitor ODQ (10 μ M , pEC 50 , 9.6±0.4) did not affect the response to bradykinin. Elevating the extracellular [K + ] to 30 m M did not affect the response to bradykinin but abolished the response when ODQ or L ‐NAME was present. The K + channel blocker apamin (100 n M ), combined with charybdotoxin (100 n M ), 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 n M ) combined with iberiotoxin (100 n M ) also reduced the response to bradykinin in the presence of hydroxocobalamin or L ‐NAME. The concentration response curve for sodium nitroprusside‐induced relaxation was abolished by ODQ (10 μ M ) and shifted to the right by apamin and charybdotoxin. 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.British Journal of Pharmacology (2002) 137 , 538–544. doi: 10.1038/sj.bjp.0704890