Sex hormones and sympathetic vascular regulation in exercising muscle

 

Gail D. Thomas

Hypertension Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas

 

Activation of the sympathetic nervous system plays an important role in the redistribution of cardiac output during exercise by causing vasconstriction in the visceral organs and non-exercising muscles to increase blood flow to the active muscles. At the same time, the normal ability of sympathetic activation to cause vasoconstriction is reduced in the active muscles. This modulation, termed functional sympatholysis, is mediated in part by an effect of muscle metabolites to attenuate alpha-adrenergic vasoconstriction in the small resistance arterioles, which may serve to optimize blood flow distribution within the active muscles. Although functional sympatholysis is readily apparent in both males and females, the underlying mechanisms may be differentially influenced by the sex hormones. Studies from our laboratory have shown that functional sympatholysis is impaired in gonadectomized female, but not male, rats. This impairment is prevented when gonadectomized female rats are treated with estradiol, but not with progesterone. Similarly, functional sympatholysis is impaired in postmenopausal women and this impairment is reversed by transdermal estradiol replacement therapy. In male rats, functional sympatholysis is impaired by treatment with an estrogen receptor antagonist and by reducing dietary phytoestrogen intake. These findings indicate that estrogens play a role in the modulation of sympathetic vasoconstriction in exercising muscle in both females and males, with a predominant effect of endogenously produced estradiol in females and of dietary phytoestrogens in males. In both sexes, these estrogenic effects may be mediated in part by an upregulation of the nitric oxide pathway in skeletal muscle. Collectively, these studies in animal and human subjects suggest that estrogens or estrogen-like compounds contribute to the sympathetic neural control of muscle blood flow during exercise.

 

Key words: estrogen, testosterone, vasoconstriction, muscle contraction