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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 297; no. 6; p. R1713
• Main Authors: LeBlanc, Amanda J, Reyes, Rafael, Kang, Lori S, Dailey, Robert A, Stallone, John N, Moningka, Natasha C, Muller-Delp, Judy M
• Format: Journal Article
• Language: English
• Published: United States 01-12-2009
• Subjects: Age Factors; Aging; Animals; Arterioles - drug effects; Coronary Circulation - drug effects; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Cyclooxygenase Inhibitors - pharmacology; Drug Implants; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Inhibitors - pharmacology; Estradiol - administration & dosage; Estrogen Replacement Therapy; Female; Hydrazines - pharmacology; Indomethacin - pharmacology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase Type III - antagonists & inhibitors; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Ovariectomy; Phosphorylation; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Inbred F344; RNA, Messenger - metabolism; Vasodilation - drug effects
• ISSN: 1522-1490
• DOI: 10.1152/ajpregu.00178.2009

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 approximately 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.