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

Abstract

October 7, 2009; 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 flowinduced 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 ϩ estrogen replaced (OVE) female Fischer-344 rats to assess flowinduced vasodilation. Advancing age impaired flow-induced dilation of coronary arterioles (young: 50 Ϯ 4 vs. old: 34 Ϯ 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 ϳ160%. 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 flowinduced vasodilation of arterioles from estrogen-replaced rats at all ages. These findings indicate that the age-induced decline of flowinduced, 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 THE RISK FOR CARDIOVASCULAR disease (CVD) and heart failure increase with advancing age; however, sexual dimorphism exists in the chronological development of these risks (22,47). Although the chronological rate of aging is independent of sex, mechanisms that regulate the cardiovascular system across the lifespan may differ dramatically between men and women. The risk for CVD in men begins to increase at approximately the same age that flow-mediated vasodilation begins to decline (5). Women also exhibit this age-related impairment of flow-mediated vasodilation; however, significant reduction of flow-mediated dilation becomes apparent at the age of menopause, more than a decade later than in men (5). The cardioprotection that women experience until menopause is presumably due to the presence of ovarian estrogen and results in a sex-related delay of the expression of CVD (49). Chronic estrogen treatment has been shown to enhance endothelial function in a number of vascular beds (27, 31, 39), in part, through a pathway involving activation of Akt/PKB and subsequent phosphorylation of endothelial nitric oxide synthase (eNOS) (3,10,15,43,44). Endothelium-dependent vasodilation to a...

Aging and estrogen alter endothelial reactivity to reactive oxygen species in coronary arterioles

“…Furthermore, elevated hydroxyl radical formation contributes to impairment of flowinduced vasodilation in coronary arterioles from aged male rats (21). Although we have reported an age-related reduction in flow-induced, NO-mediated vasodilation in coronary resistance vessels from female rats (23), the contribution of oxidant stress to this loss of NO-mediated dilation has not been determined. Therefore, we hypothesized that ROS scavenging and estrogen replacement will improve age-related impairments in flow-induced vasodilation in coronary arterioles by increasing NO bioavailability.…”

Lectin-Like Oxidized Low-Density Lipoprotein 1 Receptor in a Reduced Uteroplacental Perfusion Pressure Rat Model of Preeclampsia

“…17,[19][20][21][22][23][24][25][26]28,37,38 For instance, we verified increased systolic blood pressure, altered fetal biometrics, and glomerular endotheliosis in RUPP compared with sham-operated rats.…”

Contrasting Effects of Increased and Decreased Dopamine Transmission on Latent Inhibition in Ovariectomized Rats and Their Modulation by 17β-Estradiol: An Animal Model of Menopausal Psychosis?

“…Ovariectomy (OVX)-induced hormonal decline in rats is considered to model decreased gonadal function during menopause (Adam et al, 2009;Daniel et al, 2006;Gurkan et al, 1986;LeBlanc et al, 2009;Rogers et al, 2009;Walf et al, 2009), and has been proposed specifically to model the hormonal state associated with predisposition to schizophrenia during menopause (Bosse and Di Paolo, 1995). Although many studies showed that OVX is associated with poorer behavioral and cognitive performance, including tasks considered relevant to schizophrenia such as social interaction and object recognition (Barnes et al, 2006;Frye, 2001;Frye et al, 2006bFrye et al, , 2007Frye and Rhodes, 2006a;Paris and Frye, 2008), the study of the estrogen hypothesis using animal models of schizophrenia has been limited.…”