17 beta-Estradiol reduces vasoconstriction in endothelium-denuded rat aortas through inducible NOS.

Estrogen produces vasodilatation through the induction of nitric oxide synthase (NOS) in the endothelium, but there are many reports of endothelium-independent effects. In the present study, these processes were investigated in rat aortas isolated from ovariectomized rats. Long-term in vitro treatment with 17 beta-estradiol (10 nM for 24 h) in an organ culture system slightly reduced acetylcholine-mediated vasorelaxation in endothelium-intact aortic rings. 17 beta-Estradiol (1 and 10 nM for 24 h) also attenuated the phenylephrine-induced constriction in endothelium-denuded aortas, and this effect was inhibited by the NOS inhibitor L-N5-(1-iminoethyl)ornithine hydrochloride, as well as the estrogen receptor antagonist ICI-182,780. Furthermore, 17 beta-estradiol treatment (1 and 10 nM for 24 h) increased nitric oxide production as assessed by the conversion of [3H]arginine to [3H]citrulline in endothelium-denuded rat aortas. These effects were prevented by the protein synthesis inhibitor cycloheximide. 17 beta-Estradiol (10 nM for 24 h) treatment also induced the formation of inducible NOS (iNOS) protein in aortas. The results indicate that 17 beta-estradiol can attenuate the vasoconstrictor effect of phenylephrine by a process that involves induction of iNOS in nonendothelial cells of the aorta. We suggest that long-term estrogen therapy may induce a partial hyporesponsiveness in vascular smooth muscle via a small but sustained nitric oxide production.