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

Kang, Lori S.; Chen, Bei; Reyes, Rafael; LeBlanc, Amanda J.; Teng, Bunyen; Mustafa, S. Jamal; Muller‐Delp, Judy M.

doi:10.1152/ajpheart.00349.2010

Cited by 55 publications

(48 citation statements)

References 48 publications

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“…Similar to previous studies, we find that scavenging superoxide improves EDD in conduit and cerebral arteries from old mice (Blackwell et al 2004;Lesniewski et al 2009;Mayhan et al 2008;Modrick et al 2009) and does not affect EDD in conduit arteries from young or old CR mice (Csiszar et al 2009). However, we demonstrate that scavenging superoxide in the MCA from young and old CR mice results in reduced EDD, which is in accordance with previous studies demonstrating reactive oxygen species contribute to the dilation of resistance arteries in skeletal muscle (Sindler et al 2013;Trott et al 2011), cardiac muscle (Miura et al 2003;Feng et al 2010;Kang et al 2011), and cerebral tissue (Drouin et al 2007). Similarly, brachial artery dilation to handgrip exercise in humans, which is NO-dependent (Wray et al 2011), is improved in older adults following ingestion of an antioxidant cocktail, but is reduced in young adults after the same antioxidant cocktail .…”

Section: Oxidative Stresssupporting

confidence: 92%

Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

Walker

Henson

Reihl

et al. 2013

AGE

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Endothelial dysfunction occurs in conduit and cerebral resistance arteries with advancing age. Lifelong caloric restriction (CR) can prevent the onset of age-related dysfunction in many tissues, but its effects on cerebral resistance artery function, as compared with conduit artery function, have not been determined. We measured endothelium-dependent dilation (EDD) in the carotid artery and middle cerebral artery (MCA) from young (5-7 months), old ad libitum fed (AL, 29-32 months), and old lifelong CR (CR, 40 % CR, 29-32 months) B6D2F1 mice. Compared with young, EDD for old AL was 24 % lower in the carotid and 47 % lower in the MCA (p<0.05). For old CR, EDD was not different from young in the carotid artery (p>0.05), but was 25 % lower than young in the MCA (p<0.05). EDD was not different between groups after NO synthase inhibition with N ω -nitro-L-arginine methyl ester in the carotid artery or MCA. Superoxide production by the carotid artery and MCA was greater in old AL compared with young and old CR (p<0.05). In the carotid, incubation with the superoxide scavenger TEMPOL improved EDD for old AL (p>0.05), with no effect in young or old CR (p>0.05). In the MCA, incubation with TEMPOL or the NADPH oxidase inhibitor apocynin augmented EDD in old AL (p<0.05), but reduced EDD in young and old CR (p<0.05). Thus, age-related endothelial dysfunction is prevented by lifelong CR completely in conduit arteries, but only partially in cerebral resistance arteries. These benefits of lifelong CR on EDD result from lower oxidative stress and greater NO bioavailability.

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Section: Oxidative Stresssupporting

confidence: 92%

Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

Walker

Henson

Reihl

et al. 2013

AGE

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“…Previous work has shown in isolated coronary arterioles that endothelium-derived H 2 O 2 contributes to flow-induced vasodilation (21,22). In the present study, the contribution of H 2 O 2 to endothelium-derived vasodilation was more pronounced in arterioles from old SED rats (Fig.…”

Section: Duction Of H 2 O 2 and Ohsupporting

confidence: 61%

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

Sindler

Reyes

Chen

et al. 2013

Journal of Applied Physiology

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Sindler AL, Reyes R, Chen B, Ghosh P, Gurovich AN, Kang LS, Cardounel AJ, Delp MD, Muller-Delp JM. Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles. J Appl Physiol 114: [681][682][683][684][685][686][687][688][689][690][691][692][693] 2013. First published January 3, 2013; doi:10.1152/japplphysiol.00341.2012.-Exercise training ameliorates age-related impairments in endotheliumdependent vasodilation in skeletal muscle arterioles. Additionally, exercise training is associated with increased superoxide production. The purpose of this study was to determine the role of superoxide and superoxide-derived reactive oxygen species (ROS) signaling in mediating endothelium-dependent vasodilation of soleus muscle resistance arterioles from young and old, sedentary and exercise-trained rats. Young (3 mo) and old (22 mo) male rats were either exercise trained or remained sedentary for 10 wk. To determine the impact of ROS signaling on endothelium-dependent vasodilation, responses to acetylcholine were studied under control conditions and during the scavenging of superoxide and/or hydrogen peroxide. To determine the impact of NADPH oxidase-derived ROS, endothelium-dependent vasodilation was determined following NADPH oxidase inhibition. Reactivity to superoxide and hydrogen peroxide was also determined. Tempol, a scavenger of superoxide, and inhibitors of NADPH oxidase reduced endothelium-dependent vasodilation in all groups. Similarly, treatment with catalase and simultaneous treatment with tempol and catalase reduced endothelium-dependent vasodilation in all groups. Decomposition of peroxynitrite also reduced endothelium-dependent vasodilation. Aging had no effect on arteriolar protein content of SOD-1, catalase, or glutathione peroxidase-1; however, exercise training increased protein content of SOD-1 in young and old rats, catalase in young rats, and glutathione peroxidase-1 in old rats. These data indicate that ROS signaling is necessary for endothelium-dependent vasodilation in soleus muscle arterioles, and that exercise traininginduced enhancement of endothelial function occurs, in part, through an increase in ROS signaling. hydrogen peroxide; superoxide; peroxynitrite; nitric oxide; acetylcholine ENDOTHELIAL FUNCTION IN THE skeletal muscle resistance vasculature declines with age primarily due to decreased nitric oxide (NO) bioavailability (10,38,51,55). In feed arteries from soleus muscle, reductions in NO-dependent vasodilation are accompanied by reduced expression of endothelial NO synthase (eNOS) (65). In contrast, our laboratory has previously reported that NO-mediated vasodilation of soleus muscle arterioles declines with advancing age, despite an increase in eNOS protein levels (51). Thus the age-related decline in bioavailability of NO may be dependent on numerous other factors that regulate both NO production and degradation. eNOS activity, and subsequent NO production, is regulated by availability of substrate and cofactors, by protein-...

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“…In addition, NO has been shown to actively displace ET from its receptor binding site on VSM (12) and can directly bind to thiol groups on the ET receptor causing reduction of the thiol groups and the production of active s-nitrosothiols, a stable NO metabolite that can contribute to vasodilation (8, 33). Our laboratory has shown a decrement in NO-mediated vasodilation in coronary arterioles from aged female rats, related to decreasing circulating estrogen levels (16), whereas coronary arterioles from male rats exhibit an increase in eNOS mRNA with advancing age (32). These sex-specific NO regulatory mechanisms could contribute to the directionally opposite changes in ET-mediated constriction of coronary arterioles from aged male and female rats.…”

Section: Discussionmentioning

confidence: 99%

Divergent Effects of Aging and Sex on Vasoconstriction to Endothelin in Coronary Arterioles

et al. 2013

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The risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age-induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex-specific. Coronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor-specific signaling. In intact arterioles from males, ET-induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age-related differences in responses to ET; however, denudation of arterioles from both sexes revealed age-related differences in ETa-mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age-related changes in ET signaling occur downstream of ET receptors. Thus, aging-induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex-specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age.

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

Cited by 55 publications

References 48 publications

Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

Divergent Effects of Aging and Sex on Vasoconstriction to Endothelin in Coronary Arterioles

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