Involvement of gap junctions in bradykinin-induced relaxation of bovine pulmonary supernumerary arteries before and after inhibition of nitric oxide/guanylate cyclase.

نویسندگان

  • A Tracey
  • A MacDonald
  • A M Shaw
چکیده

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.

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عنوان ژورنال:
  • Clinical science

دوره 103 6  شماره 

صفحات  -

تاریخ انتشار 2002