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

Abstract

1. We investigated the effects of short-term exposure to physiological levels of 17β-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 17β-estradiol (1 and 30 nM) significantly attenuated vasoconstriction to endothelin-1, 5-hydroxytryptamine and U46619. Conversely, the same concentrations of testosterone significantly potentiated responses elicited by these contractile agents. These inhibitory effects of 17β-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 μM) and ICI 182,780 (10 μM), were unable to reverse the inhibitory influence 1 nM 17β-estradiol had on the agonist-mediated contractile responses. Similarly, the androgen receptor antagonists, flutamide (10 μM) and cyproterone acetate (10 μM), failed to affect the potentiating activities of 1 nM testosterone. 5. The alteration in vasoconstrictive responses observed following acute exposure to either 1 nM 17β-estradiol and 1 nM testosterone were apparent even in the presence of the protein synthesis inhibitor cycloheximide (10 μM) and the transcription inhibitor actinomycin D (10 μM). 6. In conclusion, we report a unique type of sex hormone action on the coronary vasculature. These events occur at low nanomolar concentrations of 17β-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.