17β-oestradiol enhances nitric oxide synthase activity in endothelium-denuded rat aorta

1. It has been suggested that oestrogen-produced vasodilatation is due to induction of endothelial nitric oxide synthase (NOS), but there are many reports of direct effects on vascular smooth muscle. in thr present study, these processes were investigated ia rat aorta isolated front ovariectomized rags, 2. Short-term treatment (10 min) with 17 beta-oestradiol (10 mu mol/L) produced a smalt attenuation of the phenylephrine (PE)-induced constriction, which was unaffected by the nitric oxide synthase inhibitor L-N5(-1-iminoethyl)ornithine (NIO; 100 mu mol/L), Long-term treatment (6h) with 17 beta-oestradiol (10 mu mol/L) did not affect acetylcholine-mediated vasorelaxation in endothelium-intact aortic rings, but did attenuate PE-induced constriction. This attenuation was also observed in endothelium-denuded preparations after 17 beta-oestradiol (10 mu mol/L for 6h) and was far greater than the acute effect of 17 beta-oestradiol (10 mu mol/L), 3. The attenuation produced by 17 beta-oestradiol (10 mu mol/L for Gh) was significantly inhibited by concomitant treatment with cycloheximide (1 mu mol/L), suggesting that protein synthesis vias involved, NIO (100 mu mol/L,) also attenuated the effect, which suggests that the anti-constrictor effect of 17 beta-oestradiol occurs through the increased production of nitric oxide (NO). 17 beta-Oestradiol increased NO production, as assessed by dire conversion of [H-3]-arginine to [H-3]-citrulline in rat aorta, These effects were prevented by; cycloheximide and NIO, The anti-constrictor effect of oestrogen was blocked by the oestrogen receptor antagonist ICI 182 780 (100 nmol/L), 4. Western blotting using an antibody specific for inducible nitric oxide synthase (NOS) revealed that 17 beta-oestradiol (10 mu mol/L for 24 h) treatment induced the formation of inducible NOS protein in the aorta, an effect blocked by cycloheximide. The results indicate that 17 beta-oestradiol can attenuate the vasoconstrictor effect of PE by a specific receptor-mediated process that involves induction of inducible NOS.