Published online before print March 28, 2002, doi: 10.1161/01.RES.0000016963.43856.B1
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© 2002 American Heart Association, Inc.
Integrative Physiology |
Exercise Improves Postischemic Cardiac Function in Males but Not Females
Consequences of a Novel Sex-Specific Heat Shock Protein 70 Response
From The University of Western Ontario, School of Kinesiology (Z.P., E.G.N.), Faculty of Health Sciences, Lawson Health Research Institute (E.G.N.), and the Department of Pharmacology and Toxicology (J.V.H., M.K.), Faculty of Medicine and Dentistry, London, Ontario, Canada.
Correspondence to Dr Earl Noble, School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, Ontario, Canada N6A 3K7. E-mail enoble{at}uwo.ca
Exercise is a physiological inducer of the cardioprotective heat shock protein, Hsp70. The putative biological events involved in signaling this response exhibit sexual dimorphism. Thus, it was hypothesized that exercise-mediated induction of Hsp70 would demonstrate sex specificity. After treadmill running, male rats exhibited 2-fold greater levels of cardiac Hsp70 relative to the levels in gonadally intact female rats (P<0.001). Ovariectomized female rats exhibited exercise-mediated induction of Hsp70 similar to that observed for male rats, and estrogen treatment in these female rats reversed this effect (P<0.001). Attenuation of Hsp70 signaling by estrogen was non–receptor-mediated, possibly involving a cellular membrane–stabilizing mechanism of action. The physiological importance of this sex-specific hormone-mediated stress response is underscored by the disparity in functional adaptation in response to exercise between male rats and female rats. Exercise markedly improved postischemic left ventricular developed pressure, the maximal rate of contraction, and maximal rate of relaxation, and it reduced left ventricular end-diastolic pressure in male rats (P<0.001). No such benefit of exercise was observed in intact female rats. A causal role for Hsp70 in this sex-specific cardioprotective adaptation was indicated, inasmuch as ablation of Hsp70 induction with antisense oligonucleotides designed against Hsp70 transcripts attenuated improvement in the recovery of cardiac function in exercised male rats (P<0.05). Thus, the sex-specific hormone-mediated Hsp70 response to exercise results in cardioprotective adaptation, preferentially in male rats relative to female rats. These findings suggest that exercise may be more important for males than for females in defending against the effects of heart disease and offer a novel manner by which males may reduce the sex gap in susceptibility to adverse cardiac events.
Key Words: antisense oligonucleotides • heat shock proteins • hormones • sex • stress
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