Endothelium-dependent vasorelaxation independent of nitric oxide and K+ release in isolated renal arteries of rats

1 We investigated whether K+ can act as an endothelium-derived hyperpolariz ing factor (EDHF) in isolated small renal arteries of Wistar-Kyoto rats. 2 Acetylcholine (0.001-3 muM) caused relaxations that were abolished by rem oval of the endothelium. However, acetylcholine-induced relaxations were no t affected by the nitric oxide (NO) synthase inhibitor N-omega-nitro-L-argi nine methyl ester (L-NAME, 100 muM), by L-NAME plus the soluble guanylate c yclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 1 muM) or by L-NAME plus the cyclo-oxygenase inhibitor indomethacin (10 muM). In r ings precontracted with high-K+(60 mM) physiological salt solution in the p resence of L-NAME, acetylcholine-induced relaxations were abolished. 3 L-NAME-resistant relaxations were abolished by the large-conductance Ca2-activated K+ channel inhibitor charybdotoxin plus the small-conductance Ca 2+-activated K+ channel inhibitor apamin, while the inward rectifier K+ cha nnel inhibitor Ba2+ or the gap junction inhibitor 18 alpha -glycyrrhetinic acid had no effect. Acetylcholine-induced relaxation was unchanged by ouaba in (10 muM) but was partially inhibited by a higher concentration (100 muM) . 4 In half of the tissues tested, K+(10 mM) itself produced L-NAME-resistant relaxations that were blocked by ouabain (10 muM) and partially reduced by charybdotoxin plus apamin, but not affected by 18 alpha -glycyrrhetinic ac id or Ba2+. However, K+ did not induce relaxations in endothelium-denuded t issues. 5 In conclusion, acetylcholine-induced relaxations in this tissue are large ly dependent upon hyperpolarization mechanisms that are initiated in the en dothelium but do not depend upon NO release. K+ release cannot account for endothelium-dependent relaxation and cannot be an EDHF in this artery. Howe ver, K+ itself can initiate endothelium-dependent relaxations via a differe nt pathway from acetylcholine, but the mechanisms of K+-induced relaxations remain to be clarified.