Effects of sex and estrogen on myosin COOH-terminal isoforms and contractility in rat aorta

1 Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio; and 2 Department of Physiology and Biophysics, University of Illinois Medical School at Chicago, Chicago, Illinois Submitted 10 March 2006 ; accepted in final form 18 July 2006 We reported that estrogen treatment of ovariectomized rats increased uterine smooth muscle contractility and the ratio of the COOH-terminal myosin heavy chain isoform SM1 (204 kDa) and SM2 [200 kDa; Hewett TE, Martin AF, Paul RJ. J Physiol (Lond) 460: 351–364, 1993]. We extended this model to study sex and estrogen effects on vascular contractility. Experimental groups included 10- to 14-wk-old male (M), female (F), ovariectomized female (OF), and OF treated with estrogen (OF&E) for 7 days with a subcutaneous pellet delivery system, resulting in 17 -estradiol of 85 (OF&E) vs. 5 (OF or M) pg/ml. The SM1-to-SM2 ratio increased from 1.8 to 2.6 in thoracic aorta, similar to uterine muscle. Isometric force was measured in 5-mm segments of intact and endothelium-denuded (–endo) aorta. With KCl, the maximum forces were in the order OF M > OF&E, and ED 50 OF&E > OF M. Differences in ED 50 with estrogen persisted after endothelial denudation. The decreased force in –endo OF aorta was not seen in OF&E, suggesting that estrogen altered an endothelium-dependent effect. No differences in maximum forces were noted with norepinephrine: ED 50 OF > OF&E > M. Estrogen treatment, in contrast to KCl, increased sensitivity. Endothelial denudation increased sensitivity but reduced the differences between groups. With ACh relaxation, males were more sensitive than females, and estrogen had no effect. In the abdominal aorta, there were no changes in SM1/SM2 with 17 -estradiol, and differences in contractility were blunted. In summary, estrogen treatment decreased responses to KCl but increased sensitivity to norepinephrine; male rats always demonstrated the highest contractility. An increase in the COOH-terminal myosin heavy chain isoform SM1-to-SM2 ratio with 17 -estradiol treatment may underlie the changes observed in contractility. estrogen; vascular sensitivity; isometric force; myosin isoforms; ovariectomy Address for reprint requests and other correspondence: R. J. Paul, Dept. of Molecular and Cellular Physiology, Univ. of Cincinnati College of Medicine, Cincinnati, OH 45267-0576 (e-mail: Richard.Paul{at}uc.edu )