ESTROGEN AND SELECTIVE ESTROGEN-RECEPTOR MODULATOR LY117018 ENHANCE RELEASE OF NITRIC-OXIDE IN RAT AORTA

We report on the modulatory effects of chronic subcutaneous or oral es trogen and LY117018, a selective estrogen receptor modulator, on the r elease of nitric oxide in rings of rat aorta studied under isometric c onditions. Dilator responses to acetylcholine (ACh; 10(-8) to 10(-5) M ) were obtained in phenylephrine (PE; 2 mu M)-contracted aorta, and co nstrictor dose-response curves to PE (10(-8) to 10(-5) M) were generat ed before and after pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME; 200 mu M), an inhibitor of nitric oxide synthase. Tissu e segments were obtained from five groups of rats implanted with a sub cutaneous pellet delivery system for 21 days: (1) male, (2) sham-opera ted placebo-treated female, (3) ovariectomized placebo-treated, (4) ov ariectomized, 17 beta-estradiol treated (0.5 mg/pellet) and (5) ovarie ctomized, progesterone (15 mg/pellet) and 17 beta-estradiol (0.5 mg/pe llet)-treated. Aortic rings from sham rats and ovariectomized rats rec eiving estrogen relaxed more to ACh (10(-6) to 10(-5) M) than did the rings from ovariectomized, progesterone plus estrogen-treated and male rats (P <.05). They were also characterized by a greater potentiation of the PE responses after L-NAME compared with male, progesterone plu s estrogen-treated and ovariectomized rats (P <.05) and a similar sens itivity to PE. In addition, ACh-induced relaxation and L-NAME-induced potentiation of PE contractions in aortic rings from rats dosed orally with LY117018 were similar to responses of aortic rings from rats dos ed orally with estrogen. These results demonstrate that chronically ad ministered estrogen and LY117018 enhance the release of nitric oxide f rom endothelium in rat aortic rings.