Estrogen potentiates vasopressin-induced contraction of female rat aorta by enhancing cyclooxygenase-2 and thromboxane function

Abstract

To determine the roles of estrogen and constrictor prostanoids in vasopressin (VP)-induced contraction of female rat aorta, vascular reactivity to VP was determined in thoracic aortas of intact, ovariectomized, and ovariectomized + estrogen-replaced female rats in the presence of indomethacin (Indo), NS-398, SQ-29,548, or vehicle control. The effects of estrogen on vascular reactivity to the thromboxane A2 analog U-46619 were also examined. Maximal contractile response to VP in intact female rats (5,567 ± 276 mg/mg of aortic ring wt) was markedly attenuated by ovariectomy (2,485 ± 394 mg; P < 0.001) and restored by estrogen replacement with 17β-estradiol (5,059 ± 194 mg; P > 0.1). Indo and NS-398 significantly attenuated maximal responses to VP in intact female rats to a similar extent [3,176 ± 179 ( P < 0.0001) and 3,258 ± 152 mg ( P < 0.0001), respectively]. Ovariectomy abolished and estrogen replacement restored the inhibitory effects of Indo, NS-398, and SQ-29,548. Contractile responses of rat aorta to U-46619 were significantly greater ( P < 0.0001) in females (5,040 ± 238 mg) than in males (3,679 ± 96 mg). Ovariectomy markedly attenuated (3,923 ± 84 mg; P < 0.01) and estrogen replacement restored (5,024 ± 155 mg; P > 0.1) responses to U-46619 in female aortas. These data reveal that estrogen is an important regulator of the contractile responses of female rat aorta to VP, which appears to potentiate both cyclooxygenase-2 and constrictor prostanoid function in the vascular wall.