This study evaluated the possible contribution of gap junctions to the nitric oxide (NO)- and endothelium-derived hyperpolarizing factor (EDHF)-mediated responses elicited by bradykinin in bovine pulmonary supernumerary arteries. In artery rings with an intact endothelium and treated with the cyclo-oxygenase inhibitor indomethacin (10μM), bradykinin (100pM–1μM) produced a concentration-dependent relaxation [-logEC50 (pEC50), 9.6±0.2; maximum relaxation (Rmax), 89.7±14.8%; n = 6]. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 100μM) and the NO scavenger hydroxocobalamin (200μM) each produced a rightward shift in the bradykinin concentration–response curve [pEC50: L-NAME, 8.9±0.1 (n = 6; P<0.01); hydroxocobalamin, 8.3±0.2, (n = 6; P<0.001)]. However, the soluble guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 10μM) did not significantly alter the response to bradykinin (pEC50 9.4±0.2; n = 9). The gap junction inhibitor carbenoxolone (100μM) did not affect the relaxation produced by bradykinin (pEC50, 9.7±0.1; Rmax, 100±3.2%; n = 6), but it significantly depressed Rmax when L-NAME, hydroxocobalamin or ODQ was present. Further, carbenoxolone produced a rightward shift in the bradykinin concentration–response curve in the presence of ODQ (8.4±0.1; n = 6, P<0.01). The data suggest that, in bovine pulmonary supernumerary arteries, gap junctions may, in part, facilitate the EDHF-mediated response, but not the NO-mediated response, to bradykinin. However, the additional involvement of an unidentified endothelial relaxing factor cannot be excluded.
Involvement of gap junctions in bradykinin-induced relaxation of bovine pulmonary supernumerary arteries before and after inhibition of nitric oxide/guanylate cyclase
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A. TRACEY, A. MACDONALD, A.M. SHAW; Involvement of gap junctions in bradykinin-induced relaxation of bovine pulmonary supernumerary arteries before and after inhibition of nitric oxide/guanylate cyclase. Clin Sci (Lond) 1 December 2002; 103 (6): 553–557. doi: https://doi.org/10.1042/cs1030553
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