Mechanisms of bradykinin-induced relaxation in pig coronary arteries

Bradykinin (BK) induced endothelium- and concentration-dependent relaxation s in segments of porcine posterior descending coronary arteries submaximall ly precontracted with the thromboxane A(2) mimetic, U-46619. The effects of BK were reduced by L-N-G-monomethylarginine (L-NMMA) and 6-anilinoquinolin e-5,8-quinone (LY-83583), respective inhibitors of nitric oxide (NO) syntha se and guanylate cyclase, but were unaffected by the cytochrome P450 monoxy genase blocker, thiopentone sodium; however; BK effects were slightly reduc ed by dimethyl solfoxide (DMSO), an hydroxyl radical scavenger: Relaxant re sponses were reduced markedly: bq ouabain, a sodium pump inhibitor but only slightly by tetraethylammonium (TEA) and charybdotoxin, respective blocker s of Ca-activated (K-Ca) and large-conductance (BKCa) K+ channels. However: BK responses were practically abolished by TEA + L-NMMA + ouabain while un affected by apamin, 4-aminopyridine and glibenclamide, blockers of small-co nductance K-Ca, voltage-sensitive and ATP-sensitive Kt channels, respective ly In segments submaximally precontracted with K+. BK-induced relaxation wa s letter than that of those precontracted with U-46619, and was further red uced by L-NMMA, LY-83583 and especially ouabain: L-NMMA + ouabain + TEA abo lished the effect. Precontraction of segments with higher K+ concentrations almost abolished the relaxation. These results suggest that the relaxation to BK is mediated: Ii by endothelial NO release which activates guanylate cyclase of smooth muscle cells; 2) by hydroxyl radicals: and 3) by an endot helial hyperpolarizing factor that does not seem to be a metabolite derived from cytochrome P450 monoxygenases and that relaxes activating K+ channels (mainly BKCa), and especially the sodium pump. (C) 1999 Prous Science. All rights reserved.