Contribution of K+ Channels to Relaxation Induced by 17β-Estradiol but Not by Progesterone in Isolated Rat Mesenteric Artery Rings

Abstract

17beta-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-11alpha,9alpha-epoxy-methanoprostaglandin F (U46619), the relaxation induced by 17beta-estradiol was partially inhibited by tetrapentylammonium, 4-aminopyridine, iberiotoxin, BaCl, 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 x 10(-2) K -preconstricted rings, the K channel blockers lost their inhibitory effects on 17beta-estradiol-induced relaxation. Endothelium did not seem to be involved in the effects of K channel blockers on 17beta-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 17beta-estradiol. These K channels involved in the estrogen response appeared to be sensitive to inhibition by K(Ca), K, and K(IR) 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 17beta-estradiol.

Estrogen and Tamoxifen Modulate Cerebrovascular Tone in Ovariectomized Female Rats

“…However, acute treatment with higher concentrations (Ն10 Ϫ6 mol/L) of E 2 reduces agonist-induced vasocontractions. 32 Thus, acute and nongenomic effects of estrogen and tamoxifen may differ from their long-term and genomic effects on vascular motor activity.…”

Non-genomic vasorelaxant effects of 17β-estradiol and progesterone in rat aorta are mediated by L-type Ca2+ current inhibition

“…Other authors observed that environmental estrogenic pollutants and βES induced a rapid and endothelium-independent relaxation by inhibiting LTCC in vascular smooth muscle cells [27] . Activation of K + channels by PRG and by βES in vascular smooth muscle may induce repolarization of plasma membrane, which will close the VOCCs and contribute to the vascular relaxation [27][28][29][30] . This mechanism does not appear to be very important for PRG [29] , but the opening of Ca 2+ -activated K + (BK Ca ) channels by βES has been observed in human coronary artery smooth muscle cells [30] and rat aorta A7r5 cells [27] .…”

Visceral Periadventitial Adipose Tissue Regulates Arterial Tone of Mesenteric Arteries

“…The K v channel blocker 3,4-diaminopyridine (3,4-DAP) 13 at 1 mmol/L had similar effects (nϭ5, Figure 3B and Figure IIB). The small-conductance, Ca 2ϩ -activated K ϩ channel blocker apamin 4 (1 mol/L, nϭ6; Figure 4A and Figure IIC) and the K ATP channel blocker glibenclamide 10,14 (3 mol/L, nϭ8; Figure 4B and Figure IID) were not effective. The inward rectifier K ϩ channel blocker Ba Figure IVB), and tetrapentylammonium, 17 which also blocks K ATP channels, 18 (2 mol/L, nϭ6, not shown) enhanced serotonin-dependent contractions by 20% to 30% in both (Ϫ) fat and (ϩ) fat rings.…”

“…The rings were placed in a small vessel wire myograph under an optimal resting tension of 2 mN. 3,4 Tension is expressed as a percentage of the steady-state tension (100%) obtained with isotonic external 60 mmol/L KCl.In the first series of experiments, the rings were exposed to increasing doses of serotonin (10 Ϫ8 to 10 Ϫ5 mol/L), endothelin I (10 …”

“…3,4 The periadventitial fat was removed with scissors, 2 being careful not to damage the adventitia. 5 In some experiments, 50% of the periadventitial fat was removed longitudinally along the ipsilateral side of the vessel ring with scissors; it was left intact on the contralateral side of the vessel ring.…”