Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activated potassium channel

Cardiovascular diseases are often considered to be a predominantly male hea lth problem, and it has been suggested that testosterone exerts deleterious effects on cardiovascular function; however, few experimental studies supp ort this suggestion. Moreover, the cellular and molecular mechanism(s) unde rlying vascular responses to testosterone is unknown. The present study has investigated the acute effects of testosterone on porcine coronary artery smooth muscle at the tissue and cellular levels. Contractile studies demons trated that testosterone or dihydrotestosterone (a nonaromatizable metaboli te) relaxed these arteries by an endothelium-independent mechanism involvin g potassium efflux. Direct evidence from patch-clamp studies confirmed that testosterone opened K+ channels in single coronary myocytes, and further a nalysis identified this protein as the large-conductance, calcium- and volt age-activated potassium (BKCa) channel. Moreover, inhibiting BKCa channel a ctivity significantly attenuated testosterone-induced coronary relaxation. These findings indicate that testosterone relaxes porcine coronary arteries predominantly by opening BKCa channels in coronary myocytes, and this resp onse may be associated with accumulation of cGMP. This novel mechanism may provide a better understanding of testosterone-induced vasorelaxation repor ted in recent experimental and early clinical studies.