Involvement of gap junctions in bradykinin-induced relaxation of bovine pulmonary supernumerary arteries before and after inhibition of nitric oxide/guanylate cyclase.
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 (10 microM), bradykinin (100 pM-1 microM) produced a concentration-dependent relaxation [-logEC(50) (pEC(50)), 9.6+/-0.2; maximum relaxation ( R (max)), 89.7+/-14.8%; n =6]. The NO synthase inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME; 100 microM) and the NO scavenger hydroxocobalamin (200 microM) each produced a rightward shift in the bradykinin concentration-response curve [pEC(50): 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; 10 microM) did not significantly alter the response to bradykinin (pEC(50) 9.4+/-0.2; n =9). The gap junction inhibitor carbenoxolone (100 microM) did not affect the relaxation produced by bradykinin (pEC(50), 9.7+/-0.1; R (max), 100+/-3.2%; n =6), but it significantly depressed R (max) 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.
Tracey
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School of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 OBA, UK.
MacDonald
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Shaw
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D000818:Animals; D001685:Biological Factors / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D002229:Carbenoxolone / Q000494:pharmacology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000502:physiology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006879:Hydroxocobalamin / Q000494:pharmacology; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D001685:Biological Factors; D004791:Enzyme Inhibitors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D002229:Carbenoxolone; D006879:Hydroxocobalamin; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester