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.
Binko
J
J
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Majewski
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D009924:Organ Culture Techniques; D010052:Ovariectomy; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D010656:Phenylephrine; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000109:Acetylcholine