© 1999 American Heart Association, Inc.
Editorials |
Gender, Estrogen, and NOS
Cautions About Generalizations
From the Departments of Surgery and Physiology, The Mayo Clinic and Foundation, Rochester, Minn.
Correspondence to Virginia M. Miller, PhD, The Mayo Clinic and Foundation, Departments of Surgery and Physiology, 200 First St SW, Rochester, MN 55905. E-mail miller.virginia@mayo.edu
Key Words: gender • hormones, male, female • infection • nitric oxide
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Introduction |
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Evidence from observational studies as well as prospective randomized trials indicates that the incidence of coronary artery disease is less in premenopausal women compared with age-matched men and in postmenopausal women who are using estrogen replacement therapy.1 2 The mechanisms by which estrogen reduces development of cardiovascular disease are multifactorial and, in addition to alterations in lipid metabolism, include actions on all components of the vascular wall (endothelial, smooth muscle, and adventitial cells), neurons, and blood elements (platelets and leukocytes). Changes in production of nitric oxide (NO) have been implicated as one of the cellular biochemical-related pathways regulated by estrogen that may contribute to gender and hormonal differences in the progression of cardiovascular disease.3 4 5 6 7 8 9 NO is synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). NOS consists of three isoforms: type I, neuronal; type II, inducible; and type III, endothelial/constitutive. In this issue of Circulation Research, García-Durán et al10 add to the accumulating body of evidence suggesting that estrogen directly modulates expression of NOS, in particular the neuronal isoform (type I) in neutrophils. With use of Western blot analysis of protein isolated from neutrophils, levels of neuronal NOS were greater in neutrophils from premenopausal women during the ovulatory phase of the estrus cycle when estrogen is high compared with the follicular phase when circulating levels of estrogen fall. In addition, expression of neuronal NOS increased in neutrophils of postmenopausal women who were using transdermal estrogen replacement (50 mg/d) for 4 months. The range of circulating estrogen over which
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