Vasorelaxation Effect of Estrone Derivate EA204 in Rabbit Aorta

Abstract

Estrogen and its derivatives exert vascular protective effects, but the underlying mechanisms remain to be studied fully. Objective. To investigate the vasorelaxation effect and related mechanisms of an estrone derivate EA204[3-(2-piperidin-1-yl)-ethoxy-estra-1, 3, 5 (10)-trien-17-one] on isolated arterial preparation from rabbit thoracic aorta. Methods. Aortic rings from rabbit thoracic aorta were prepared and held in small organ bath filled with Krebs solution; tension change was recorded by a multichannel physiological signal collection and handling system. Results. EA204 (10−5 to 10−3 M) induced a concentration-dependent relaxation of aortic rings with endothelium and without endothelium. In denuded arterial preparations, EA204 had a potent relaxing effect on isolated arterial preparations contracted with phenylephrine, norepinephrine, and high-K+ solution or BaCl2. Mechanism study indicates that EA204 relaxes aortic rings by inhibiting Ca2+ channels (both receptor-operating Ca2+ channels and the voltage-dependent Ca2+ channels were involved) to decrease extracellular Ca2+ influx and intracellular Ca2+ release. EA204 is different from verapamil, which is a noncompetitive inhibitor of Ca2+ channels. In addition, K+ channels opening may contribute to this vasorelaxation effect. Conclusion. EA204 had a potent endothelium-independent relaxing effect on isolated arterial preparation by inhibiting Ca2+ channels and opening K+ channels. The results suggest that EA204 is a potential compound for treatment of cardiovascular diseases in postmenopausal women.