Testosterone and Cholesterol Vasodilation of Rat Aorta Involves L-Type Calcium Channel Inhibition

Abstract

Testosterone has rapid nongenomic vasodilator effects which could be involved in protective cardiovascular actions. Several authors suggested specific mechanisms to explain this effect, but this matter was not clarified yet. We studied the actions of testosterone and cholesterol on endothelium-denuded rat aorta and their effects on the L-type Ca2+ current (ICa,L) and potassium current (IK). Testosterone (1–100 μM) totally relaxed, in a rapid and concentration-dependent way, the aortic rings contracted by KCl or by (−)-Bay K8644 (BAY). Cholesterol also fully relaxed the contractions induced by KCl. None of the potassium channel antagonists tested (glibenclamide, tetraethylammonium and 4-aminopyridine) modified significantly the relaxant effect of testosterone. The antagonist of classic testosterone receptors, flutamide, did not modify the vasorelaxant effect of testosterone. Furthermore, testosterone and cholesterol inhibited either basal and BAY-stimulated ICa,L in A7r5 cells and they have no effects on IK. In summary, our results demonstrate that cholesterol and testosterone relax rat aorta by inhibiting LTCC. This effect of testosterone is not mediated by the classic hormone receptor or by potassium channel activation. These results suggest that the vasodilator mechanism of cholesterol and testosterone is the same.

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

“…The potassium current measured was significantly inhibited by the K V channel blocker (4-AP) and by the BK Ca channel blocker (TEA), but the SK Ca (low conductance) channel blocker (apamine) and the K ATP channel blocker (glibenclamide) did not have a significant effect on the potassium current measured. In agreement with previous data [37] , our study show that the potassium current measured in A7r5 cells is mainly due to K V and BK Ca channels. On the other hand, for the first time our study also demonstrates that βES and PRG fail to stimulate I K in A7r5 cells.…”

“…In opposition, Rodriguez et al showed that 17α-estradiol, but not βES, relaxes calcium-dependent contractions in rat aortic strip [36] . On the other hand, we previously showed that testosterone and cholesterol also relax rat aorta by inhibiting LTCC [37] . Thus, in the sense, the vasodilator effect of cholesterol, testosterone, βES and PRG seems to be similar.…”

Hormonal effects on blood vessels

“…Similar results have been reported in different experimental conditions by other groups. [106][107][108] The involvement of potassium channels in testosterone-induced vasodilatation has also been studied by many researchers. [109][110][111] Cairrao et al 112 reported that an AR antagonist, flutamide, and an adenosine triphosphate-sensitive potassium-channel inhibitor, glibenclamide, had no influence on the testosterone relaxant effect, whereas a voltage-sensitive potassium-channel inhibitor, 4-aminopyridine, decreased this effect of testosterone.…”

Testosterone and Atrial Natriuretic Peptide Share the Same Pathway to Induce Vasorelaxation of Human Umbilical Artery

“…[2][3][4] However, the cellular and molecular mechanisms involved in the effect are not yet fully understood. [6][7][8] The inhibition of voltage-dependent calcium channels by testosterone was also demonstrated in vascular smooth muscle (VSM) from distinct animals. 2,5,6 Most of the signaling pathways involved in this direct effect of androgens are related to the modulation of ionic fluxes.…”

“…Various authors suggested that testosterone induces vascular relaxation by a nongenomic mechanisms. [8][9][10] However, several authors showed that androgens could activate different types of potassium channels in distinct arteries and induce vasodilatation. Several authors showed that androgens could inhibit different types of calcium channels in different vessels.…”