Effect of 17β-Estradiol Exposure on Vasorelaxation Induced by K⁺ Channel Openers and Ca²⁺ Channel Blockers

Abstract

17β-Estradiol has been shown to relax blood vessels partly through inhibition of Ca²⁺ channels at supraphysiological concentrations; however, it is unknown whether acute exposure of the isolated artery rings to near physiological concentrations of sex steroid hormones could modulate the ionic channels that are involved in regulation of vascular tone. Brief incubation (20 min) with 17β-estradiol (1–3 nmol/l) did not alter the relaxant response to three blocking agents of L-type voltage-sensitive Ca²⁺ channels, nifedipine, diltiazem and verapamil in either endothelium-intact or endothelium-denuded rat mesenteric artery rings. In contrast, 17β-estradiol at 3 nmol/l significantly attenuated the relaxation induced by K⁺ channel openers, cromakalim and pinacidil in endothelium-denuded rings. Similarly, preincubation with progesterone (3 nmol/l) inhibited pinacidil-induced relaxation with much less effect on cromakalim-induced relaxation. It appears that 17β-estradiol and progesterone attenuated the cromakalim- and pinacidil-induced relaxation in a different manner. These results suggest that acute exposure to female sex steroid hormones at near physiological levels may reduce the activity of ATP-sensitive K⁺ channels in the rat arteries.

Influence of sex steroid hormones on cerebrovascular function

“…"Classical" sex steroid receptors are nuclear receptors that modulate gene expression in concert with other transcription factors that are often tissue specific (71). Additional "nongenomic" effects of gonadal hormones appear to be mediated via ion channels, membrane receptors, and cellular signaling pathways (53,81,106,127).…”