The role of gap junctions in mediating endothelium-dependent responses to bradykinin in myometrial small arteries isolated from pregnant women.

Endothelium-dependent responses were assessed in myometrial small arteries isolated from pregnant women, using pressure myography. Responses to bradykinin were unaffected by the combined presence of the nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 100 micro M) and the cyclo-oxygenase inhibitor, indomethacin (10 micro M). The additional presence of clotrimazole (50 micro M) attenuated, but did not abolish, vasodilator responses to bradykinin. Raising extracellular [K(+)] (by between 1 and 15 mM) did not evoke a vasodilator response, nor did the cannabinoids, anandamide and methanandamide. Responses to bradykinin were attenuated in the presence of the gap junction inhibitors 18-alpha-glycyrrhetinic acid (18-alpha GA, 100 micro M), carbenoxolone (100 micro M) and palmitoleic acid (50 micro M). SR141716A, the CB(1) receptor antagonist attenuated responses to bradykinin, but only at high concentrations (10 micro M). These results suggest that gap junctional communication is involved in the nitric oxide (NO)- and prostanoid-independent vasodilator responses to bradykinin in myometrial small arteries in normal pregnancy.