Differential effects of 17β-estradiol and testosterone on the contractile responses of porcine coronary arteries

1 We investigated the effects of short-term exposure to physiological levels of 17 beta-estradiol and testosterone on vasocontractile responses in porcine coronary artery rings. 2 Concentration-response curves to endothelin-1, 5-hydroxytryptamine, the thromboxane analogue U46619 and KCl were constructed in endothelium-intact and endothelium-disrupted artery rings. 3 Thirty minutes exposure to 17 beta-estradiol (1 and 30 nM) significantly attenuated vasoconstriction to endothelin-l, 5-hydroxytryptamine and U46619. Conversely, the same concentrations of testosterone significantly potentiated responses elicited by these contractile agents. These inhibitory effects of 17 beta-estradiol and enhancing actions of testosterone on contractions were endothelium-independent. KCl-mediated contractions were unaffected by the presence of either sex hormones. 4 The oestrogen receptor antagonists, tamoxifen (10 mu M) and ICI 182,780 (10 mu M), were unable to reverse the inhibitory influence 1 nM 17 beta-estradiol had on the agonist-mediated contractile responses. Similarly, the androgen receptor antagonists, flutamide (10 mu M) and cyproterone acetate (10 mu M), failed to affect the potentiating activities of I nM testosterone. 5 The alteration in vasoconstrictive responses observed following acute exposure to either 1 nM 17 beta-estradiol and 1 nM testosterone were apparent even in the presence of the protein synthesis inhibitor cycloheximide (10 mu M) and the transcription inhibitor actinomycin D (10 mu M). 6 In conclusion, we report a unique type of sex hormone action on the coronary vasculature. These events occur at low nanomolar concentrations of 17 mu-estradiol and testosterone, are insensitive to conventional sex hormone receptor antagonists, are not blocked by de novo protein synthesis inhibitors and have rapid time-courses that are uncharacteristic of classical genomic activities.