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