The acute estrogenic dilation of rat aorta is mediated solely by selective estrogen receptor ERalpha agonists and is abolished by estrogen deprivation

Estrogen is known to induce rapid vasodilatory response in isolated arteries. Because estrogen is a nonselective receptor agonist, the involvement of estrogen receptor (ER) subtypes in acute estrogenic responses has remained elusive. Acute administration of the selective ER? agonist PPT to precontracted aortic rings from intact female rats dose-dependently induced an ER-dependent vascular relaxation fully overlapping to that induced by 17?-estradiol. By contrast, the selective ER? agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) had no acute effect on vasomotion. This short-term vasorelaxant action of PPT was abolished by the NO synthase inhibitor N?-nitro-L-argininemethyl ester and by endothelium removal. In aortic tissues from ovariectomized (OVX) rats, however, neither 17?-estradiol nor PPT induced acute vascular relaxation. The effect of PPT was restored in prepns. from estrogen-replaced OVX rats, whereas DPN remained ineffective even after estrogen replacement. PPT acted through an ER-dependent mechanism, as shown by impaired response in the presence of the anti-estrogen ICI 182,780. Accordingly, isolated rat aortic endothelial cells expressed both ER? and ER?. These data show that selective ER? but not ER? agonists reproduced the acute vasodilation of estrogen via a receptor-mediated pathway in the aorta from intact as well as 17?-estradiol-replaced OVX rats. This beneficial effect was undetectable in tissues from OVX rats. Selective pharmacol. targeting of ER subtypes may thus represent a novel and promising approach in the treatment of vascular disease.