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Endothelium-Dependent and Independent Enhancement of Vascular Contractility in the Ovariectomized Rabbit

Katsuya Hirano, MD,PhD

Junji Nishimura, MD,PhD

Hitoo Nakano, MD,PhD

Division of Molecular Cardiology, Research Institute of Angiocardiology, and Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Hideo Kanaide, MD,PhD

Division of Molecular Cardiology, Research Institute of Angiocardiology, and Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; kanaide{at}molcar.med.kyushu-u.ac.jp

Objective: Estrogen suppresses contractile response and increases vasodilator response, partly by modulating endothelial function. However, the effect of estrogen on the contractility of vascular smooth muscle remains to be elucidated. We investigated the effect of a long-term estrogen deficiency on vascular contractility and the Ca²⁺ sensitivity of the contractile apparatus in arterial smooth muscle.

Methods: Female rabbits were divided into the following three groups: control group, an ovariectomized group (OVX), and a group supplemented with 17ß-estradiol after ovariectomy (OVX+E2). Twelve weeks later, the mesenteric artery was isolated, and the vascular contractility was evaluated.

Results: In OVX, the contractile responses to phenylephrine and 118 mM postassium were enhanced, and the basal release of nitric oxide decreased in the strips with endothelium compared with either OVX+E2 or control. An enhancement of contraction was also observed in the strips without endothelium. However, the extent of enhancement was smaller than that observed in the presence of endothelium. The simultaneous measurement of calcium ([Ca²⁺]_i) and tension revealed no significant difference in the [Ca²⁺]_i elevations induced by phenylephrine among the three groups. In the -toxin permeabilized strips, the Ca²⁺-tension relationships obtained both with and without phenylephrine and guanosine triphosphate were similar among the three groups. No difference in the myosin expression and the histology of vascular tissue was observed among the three groups.

Conclusion: Long-term estrogen deficiency increased the vascular tone mainly by enhancing smooth muscle contractility. Endothelial dysfunction is considered to play a minor role in the augmentation of vascular tone.

Key Words: Estrogen • endothelial cells • contraction • rabbit • mesenteric artery

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 5, 272-279 (2004)
DOI: 10.1016/j.jsgi.2004.03.002


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