TESTOSTERONE RELAXES RABBIT CORONARY-ARTERIES AND AORTA

Background Until menopause, women appear to be protected from coronary heart disease. Evidence suggests that estrogen may play a role in the protection of the cardiovascular system by exerting a beneficial effe ct on risk factors such as cholesterol metabolism and by a direct effe ct on the coronary arteries. To date there has been no evidence linkin g testosterone with the occurrence of coronary heart disease. Testoste rone may affect the cardiovascular system directly, thus partially exp laining the difference in the incidence of coronary artery disease in men and premenopausal women. The purpose of this study was to assess t he direct effect of testosterone and a number of testosterone analogue s on rabbit coronary arteries and aorta in vitro. Methods and Results Rings of coronary artery and aorta of adult male or nonpregnant female New Zealand White rabbits were suspended in organ baths containing Kr ebs solution; isometric tension then was measured. The response to tes tosterone was investigated in prostaglandin F-2 alpha (PGF(2 alpha)- a nd KCl-contracted rings. The effects of endothelium and nitric oxide s ynthase, prostaglandin synthetase, and guanylate cyclase inhibition on testosterone-induced relaxation were investigated. The effects of ATP -sensitive potassium channels and potassium conductance were also asse ssed. Relaxing responses in the presence of aromatase inhibition and t estosterone receptor blockade were performed. The relaxing responses t o the testosterone analogues etiocholan-3 beta-ol-17-one, epiandroster one, 17 beta-hydroxy-5 alpha-androst-1-en-3-one, androst-16-en-3-ol, a nd testosterone enanthanate were measured. Testosterone relaxed rabbit coronary arteries and aorta. There was no significant difference betw een the relaxation effect of testosterone with or without endothelium. Similar results were obtained from male and nonpregnant female rabbit s. The relaxing response of testosterone in the coronary artery was si gnificantly greater than in the aorta. The relaxing response of testos terone in the coronary artery was significantly reduced by the potassi um channel inhibitor barium chloride but not by the ATP-sensitive pota ssium channel inhibitor glibenclamide. The relaxing response to testos terone was greater in PGF(2 alpha)-contracted rings compared with KCl- contracted rings. Inhibitors of nitric oxide synthase, prostaglandin s ynthetase, and guanylate cyclase did not affect relaxation induced by testosterone. Inhibition of aromatase and testosterone receptors did n ot affect relaxation. Testosterone did not shift the rabbit coronary a rterial calcium concentration-dependent contraction curves, whereas ve rapamil did. There were, however, significant differences in the relax ing response to testosterone compared with testosterone analogues. Tes tosterone was the most potent relaxing agent, suggesting that there ma y be a structure-function relation in the relaxing response. Conclusio ns Testosterone induces endothelium-independent relaxation in isolated rabbit coronary artery and aorta, which is neither mediated by prosta glandin I-2 or cyclic GMP. Potassium conductance and potassium channel s but not ATP-sensitive potassium channels may be involved partially i n the mechanism of testosterone-induced relaxation. The in vitro relax ation is independent of sex and of a classic receptor. The coronary ar tery is significantly more sensitive to relaxation by testosterone tha n the aorta. Testosterone is a more potent relaxing agent of rabbit co ronary artery than other testosterone analogues.