Acute impairment of relaxation by low levels of testosterone in porcine coronary arteries

Objectives: While there are many suggested reasons for the marked gender bi as in cardiovascular events, much of the available data indicate that circu lating estrogens are cardioprotective. The possibility that endogenous andr ogens may be detrimental to the cardiovascular system has received relative ly less attention. We investigated the short-term modulatory effects of var ious concentrations of testosterone on vascular function in isolated porcin e coronary artery rings. Results: The higher concentrations (>1 mu M) of te stosterone relaxed U46619-contracted coronary artery rings in an endotheliu m-independence manner. This direct effect was insensitive to the testostero ne receptor antagonists, flutamide and cyproterone acetate. Short-term expo sure (20 min) to low levels of testosterone (1-100 nM), which were ineffect ive on their own on vascular function, significantly diminished relaxation to bradykinin and calcium ionophore A23187 but not those produced by levcro makalim and sodium nitroprusside. The inhibitory effect observed with 1 nM testosterone was only partially reversed by flutamide and cyproterone aceta te and unaltered in the presence of actinomycin D and cycloheximide. Conclu sions: These results demonstrate that acute treatment with testosterone, at concentrations that have no effect on their own, reduces vasorelaxation. F urthermore, they suggest that this modulatory action may be in part indepen dent of the classical testosterone receptor since it was not completely sen sitive to the anti-androgens and was not inhibited by the transcriptional a nd translational inhibitors. These finding support the postulation that tes tosterone may have unfavorable influences on vascular function, (C) 2000 El sevier Science B.V. All rights reserved.