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Am J Physiol Heart Circ Physiol 287: H1950-H1956, 2004. First published July 1, 2004; doi:10.1152/ajpheart.00341.2004
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Estrogen replacement suppresses stress-induced cardiovascular responses in ovariectomized rats

Keiko Morimoto,1 Youko Kurahashi,1 Kaori Shintani-Ishida,2 Natsuko Kawamura,1 Mariko Miyashita,1 Masami Uji,1 Nobusuke Tan,3 and Ken-ichi Yoshida2

1Department of Environmental Health, Faculty of Life Science and Human Technology, Nara Women's University, Nara 630-8506; 2Department of Forensic Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033; and 3Department of Exercise and Health Science, Faculty of Education, Yamaguchi University, Yamaguchi 753-8513, Japan

Submitted 15 April 2004 ; accepted in final form 30 June 2004

We assessed the hypothesis that chronic estrogen replacement in ovariectomized rats has the beneficial effect of suppressing stress-induced cardiovascular responses through endothelial nitric oxide synthase (eNOS). We employed a radiotelemetry system to measure blood pressure and heart rate (HR). Female Wistar rats aged 11 wk were ovariectomized and implanted with radiotelemetry devices. After 4 wk, the rats were assigned either to a placebo-treated group (Placebo; n = 6) or a group treated with 17{beta}-estradiol (Estrogen; n = 8) subcutaneously implanted with either placebo- or 17{beta}-estradiol (1.5 mg/60-day release) pellets under anesthesia. These rats underwent either of the two types of stress after 4 wk of estrogen or placebo treatment. Cage-switch stress and restraint stress rapidly and continuously elevated the mean arterial pressure (MAP) and HR both in the Placebo and Estrogen groups. However, the MAP and HR responses to cage-switch stress and the MAP but not HR response to restraint stress were attenuated significantly in the Estrogen group compared with the Placebo group. A NOS inhibitor, NG-nitro-L-arginine methyl ester, given in drinking water, reduced the difference in the pressor response to cage-switch between the Estrogen and Placebo groups. In addition, Western blot analysis showed that eNOS expression in the mesentery was increased in the Estrogen group compared with the Placebo group. Thus for the first time we showed that mesenteric eNOS overexpression could explain at least partly why chronic estrogen treatment suppressed the enhanced cardiovascular responses to psychological stress in the ovariectomized rat.

nitric oxide synthase; blood pressure; heart rate; radiotelemetry and psychological stress



Address for reprint requests and other correspondence: K. Morimoto, Dept. of Environmental Health, Faculty of Life Science and Human Technology, Nara Women's University, Kita-Uoya Nishi-machi, Nara 630-8506, Japan (E-mail: kmorimot{at}cc.nara-wu.ac.jp)




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