CALL FOR PAPERS Sex Differences in Renal and Cardiovascular Function: Physiology and Pathophysiology Hypersensitivity of myofilament response to Ca in association with maladaptation of estrogen-deficient heart under diabetes complication

Thawornkaiwong A, Pantharanontaga J, Wattanapermpool J. Hypersensitivity of myofilament response to Ca in association with maladaptation of estrogen-deficient heart under diabetes complication. Am J Physiol Regul Integr Comp Physiol 292: R844–R851, 2007. First published October 12, 2006; doi:10.1152/ajpregu.00365.2006.— The amelioration of cardioprotective effect of estrogen in diabetes suggests potential interactive action of estrogen and insulin on myofilament activation. We compared Ca -dependent Mg -ATPase activity of isolated myofibrillar preparations from hearts of sham and 10-wk ovariectomized rats with or without simultaneous 8 wk-induction of diabetes and from diabetic-ovariectomized rats with estrogen and/or insulin supplementation. Similar magnitude of suppressed maximum myofibrillar ATPase activity was demonstrated in ovariectomized, diabetic, and diabetic-ovariectomized rat hearts. Such suppressed activity and the relative suppression in -myosin heavy chain level in ovariectomy combined with diabetes could be completely restored by estrogen and insulin supplementation. Conversely, the myofilament Ca hypersensitivity detected only in the ovariectomized but not diabetic group was also observed in diabetic-ovariectomized rats, which was restored upon estrogen supplementation. Binding kinetics of 1-adrenergic receptors and immunoblots of 1-adrenoceptors as well as heat shock 72 (HSP72) were analyzed to determine the association of changes in receptors and HSP72 to that of the myofilament response to Ca . The amount of 1-adrenoceptors significantly increased concomitant with Ca hypersensitivity of the myofilament, without differences in the receptor binding affinity among the groups. In contrast, changes in HSP72 paralleled that of maximum myofibrillar ATPase activity. These results indicate that hypersensitivity of cardiac myofilament to Ca is specifically induced in ovariectomized rats even under diabetes complication and that alterations in the expression of 1-adrenoceptors may, in part, play a mechanistic role underlying the cardioprotective effects of estrogen that act together with Ca hypersensitivity of the myofilament in determining the gender difference in cardiac activation.