Contribution of K⁺ channels to relaxation induced by 17β-estradiol but not by progesterone in isolated rat mesenteric artery rings

17β-Estradiol and progesterone were found to relax various vascular beds through multiple mechanisms. However, the exact ionic mechanisms underlying the acute relaxant responses to both hormones are incompletely understood. This study was aimed to examine the possible role of K⁺ channel activation in the relaxation induced by both hormones in isolated rat mesenteric artery rings. Isometric tension of each ring was measured with Grass force displacement transducers. In rat endothelium-denuded rings preconstricted by 9,11-dideoxy-11α,9α-epoxy-methanoprostaglandin F_2α (U46619), the relaxation induced by 17β-estradiol was partially inhibited by tetrapentylammonium, 4-aminopyridine, iberiotoxin, BaCl₂, and tertiapin-Q but not by tetraethylammonium, charybdotoxin, apamin, or glibenclamide. In contrast, these putative K⁺ channel blockers, except for glibenclamide, did not affect the relaxant response to progesterone. In 4 × 10^-2 M K⁺-preconstricted rings, the K⁺ channel blockers lost their inhibitory effects on 17β-estradiol-induced relaxation. Endothelium did not seem to be involved in the effects of K⁺ channel blockers on 17β-estradiol-mediated relaxation. Nifedipine-induced relaxation was not inhibited but was instead enhanced by tetrapentylammonium, iberiotoxin, 4-aminopyridine, and BaCl₂. The above results indicate that in rat mesenteric artery rings, nonselective activation of K⁺ channels contributes partially to the relaxation induced by 17β-estradiol. These K⁺ channels involved in the estrogen response appeared to be sensitive to inhibition by K_Ca, K_V, and K_1R channel blockers. Lack of effect of K⁺ channel blockers on progesterone-induced relaxation suggests that these K⁺ channels play little or no role. The present findings provide pharmacological evidence for an additional mechanism contributing to acute vasorelaxation induced by 17β-estradiol.