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.
Highlights
Gender differences in the incidence of cardiovascular health problems were attributed to different sex hormonal patterns found in women and men
We analyzed the effect of testosterone and cholesterol on endothelium-denuded rat aorta contracted arteries and on the ICa,L and IK measured by whole cell voltage-clamp in A7r5 cells
The vasorelaxant effect of testosterone in rat denuded aortic rings contracted with KCl was concentration-dependent and the maximal relaxation effect obtained was 100%, data that are in agreement with the obtained by Tep-areenan et al [14]
Summary
Gender differences in the incidence of cardiovascular health problems were attributed to different sex hormonal patterns found in women and men. Some studies and clinical trials suggested a direct modulation of vascular function by both female and male sex hormones [1]. Testosterone was associated with negative effects on the cardiovascular system, such as increased cardiovascular disease risk, thrombosis, cardiac hypertrophy, and suspected proatherogenic effects [2, 3]. More recent studies illustrated that testosterone has some beneficial cardiovascular effects and several epidemiological studies indicated that patients with cardiovascular diseases have low levels of testosterone [4,5,6,7]. High cholesterolemia was related with the increase in cardiovascular diseases. Some studies attempting to link hypercholesterolemia with abnormal vascular smooth muscle (SMC) contractions have focused on the endothelium
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