Testosterone is a potent inhibitor of L-type Ca2+ channels

Testosterone administration is beneficial in alleviating myocardial ischaemia in men with significant coronary artery disease (CAD), a condition which is associated with hypotestosteronaemia. Infusion of physiological concentrations of testosterone into coronary arteries at angiography results in rapid vasodilatation in patients with CAD. Whilst the cardiovascular benefits of testosterone have long been documented, the underlying mechanism(s) have not yet been revealed. Here, we have investigated whether testosterone might act like widely prescribed antihypertensive dihydropyridines, as an endogenous Ca2+ channel antagonist. To do this, we used the whole-cell patch-clamp technique to record Ca2+ Currents from the A7r5 smooth muscle cell line and HEK 293 cells stably expressing either L- or T-type Ca2+ channels. We demonstrate that testosterone directly inhibited both native and human recombinant vascular L-type Ca2+ channels in a manner that was voltage-independent and, crucially, displayed an IC50 value of 38 nM, a value within the physiological range. At higher (supraphysiological) concentrations both native and human recombinant T-type channels were also inhibited by testosterone. Our data indicate that testosterone acts like widely prescribed antihypertensive dihydropyridines to reduce Ca2+ influx into vascular smooth muscle and so promote vasodilation. This effect is likely to account for its beneficial cardiovascular actions. (C) 2004 Elsevier Inc. All rights reserved.