Effects of estrogen on the microcirculation and thrombus formation in pial vessels of the rat

Abstract

Female Wistar/ST rats were ovariectomized at 14 weeks of age. Ethynylestradiol, 17β-estradiol (E 2β), medroxyprogesterone acetate (MPA) and 4-hydroxy-tamoxifen were administered subcutaneously every other day for 3 weeks from 1 week after ovariectomy. Closed cranial windows were created and the thrombotic potential was measured using the He–Ne laser-induced thrombosis method. The mean red cell velocity was measured with a fiber-optic laser-Doppler anemometer microscope. The plasma concentrations of nitrite/nitrate (nitric oxide (NO) metabolites) were determined using the Griess reagent. The diameters mean red cell velocity and blood flow in pial arterioles were reduced after ovariectomy, however, the thrombotic tendency was increased after ovariectomy. These parameters were reversed after E 2β treatment. In contrast, MPA had the opposite effects. The plasma concentrations of nitrite/nitrate were significantly decreased following ovariectomy and were increased after treatment with E 2β. MPA did not affect the concentration of NO metabolites. These results strongly indicated that estrogen in the female rat mediated beneficial effects on the cerebral microcirculation and moderated cerebral thrombotic mechanisms by enhancing the plasma levels of NO. The findings suggest that increased blood flow and inhibition of thrombosis might contribute to the prevention of cerebrovascular disease in a normal female.