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This Article Full Text Full Text (PDF) All Versions of this Article: 297/6/R1713    most recent 00178.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by LeBlanc, A. J. Articles by Muller-Delp, J. M. PubMed PubMed Citation Articles by LeBlanc, A. J. Articles by Muller-Delp, J. M.

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Estrogen replacement restores flow-induced vasodilation in coronary arterioles of aged and ovariectomized rats

¹Center for Cardiovascular and Respiratory Sciences, ²Division of Exercise Physiology, School of Medicine, ³Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, West Virginia; ⁴Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, Texas; and ⁵Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, Florida

Submitted March 27, 2009 ; accepted in final form October 5, 2009

The risk for cardiovascular disease (CVD) increases with advancing age; however, the age at which CVD risk increases significantly is delayed by more than a decade in women compared with men. This cardioprotection, which women experience until menopause, is presumably due to the presence of ovarian hormones, in particular, estrogen. The purpose of this study was to determine how age and ovarian hormones affect flow-induced vasodilation in the coronary resistance vasculature. Coronary arterioles were isolated from young (6 mo), middle-aged (14 mo), and old (24 mo) intact, ovariectomized (OVX), and ovariectomized + estrogen replaced (OVE) female Fischer-344 rats to assess flow-induced vasodilation. Advancing age impaired flow-induced dilation of coronary arterioles (young: 50 ± 4 vs. old: 34 ± 6; % relaxation). Ovariectomy reduced flow-induced dilation in arterioles from young females, and estrogen replacement restored vasodilation to flow. In aged females, flow-induced vasodilation of arterioles was unaltered by OVX; however, estrogen replacement improved flow-induced dilation by 160%. The contribution of nitric oxide (NO) to flow-induced dilation, assessed by nitric oxide synthase (NOS) inhibition with N^G-nitro-L-arginine methyl ester (L-NAME), declined with age. L-NAME did not alter flow-induced vasodilation in arterioles from OVX rats, regardless of age. In contrast, L-NAME reduced flow-induced vasodilation of arterioles from estrogen-replaced rats at all ages. These findings indicate that the age-induced decline of flow-induced, NO-mediated dilation in coronary arterioles of female rats is related, in part, to a loss of ovarian estrogen, and estrogen supplementation can improve flow-induced dilation, even at an advanced age.

endothelial nitric oxide synthase; Akt; nitric oxide; ovariectomy