Abstract

The risk for heart disease increases dramatically with advancing age. Before the age of menopause, the risk for heart disease in women is reduced compared to that of men; however, after menopause the risk in women increases to a level greater than that of men. Although an age related decrease in coronary blood flow capacity may contribute to the increased risk of heart disease in both males and females, little is known of the interactive effects of age and estrogen on vasoreactivity of the coronary resistance vasculature, the major site for control of coronary blood flow. Recent work indicates that age impairs endothelium-dependent, nitric oxide (NO)-mediated vasodilation of coronary resistance arterioles from both male and female rats; however, preliminary data suggest that the mechanistic changes that result in impaired NO-mediated dilation differ between genders. Therefore, the overall aim of this proposal is to determine the mechanisms by which age and estrogen status alter endothelium dependent, NO-mediated vasodilation in coronary arterioles.
Aim 1 is to determine the effect of age and estrogen status on cellular signaling mechanisms that regulate NO-mediated dilation in coronary arterioles.
Aim 2 is to determine the effects of age and estrogen status on the contribution of nitric oxide synthase (NOS) isoforms to endothelium-dependent dilation and the activity of (NOS) isoforms in coronary arterioles.
Aim 3 is to determine the effects of age and estrogen status on mRNA and protein expression of NOS isoforms in coronary arterioles. These studies will identify mechanisms that contribute to the age-related impairment of NO-mediated vasodilation and determine whether estrogen treatment can improve NO-mediated vasodilation thru restoration of these signaling mechanisms. The information gained from this work will increase our understanding of the effects of age and estrogen in the coronary resistance vasculature and provide insight into the mechanisms that contribute to the age-related loss of endothelial function in both males and females. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL077224-05
Application #
7391188
Study Section
Special Emphasis Panel (ZRG1-CMAD (01))
Program Officer
Liang, Isabella Y
Project Start
2005-04-15
Project End
2008-09-30
Budget Start
2008-04-01
Budget End
2008-09-30
Support Year
5
Fiscal Year
2008
Total Cost
$108,225
Indirect Cost

  Institution

Name
West Virginia University
Department
Physiology
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506

  Publications

Hotta, Kazuki; Chen, Bei; Behnke, Bradley J et al. (2017) Exercise training reverses age-induced diastolic dysfunction and restores coronary microvascular function. J Physiol 595:3703-3719
Ghosh, Payal; Mora Solis, Fredy R; Dominguez 2nd, James M et al. (2015) Exercise training reverses aging-induced impairment of myogenic constriction in skeletal muscle arterioles. J Appl Physiol (1985) 118:904-11
Hanna, Mina A; Taylor, Curtis R; Chen, Bei et al. (2014) Structural remodeling of coronary resistance arteries: effects of age and exercise training. J Appl Physiol (1985) 117:616-23
Sindler, Amy L; Reyes, Rafael; Chen, Bei et al. (2013) Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles. J Appl Physiol (1985) 114:681-93
Leblanc, Aj; Chen, B; Dougherty, Pj et al. (2012) Divergent effects of aging and sex on vasoconstriction to endothelin in coronary arterioles. Microcirculation :
Sasser, Jennifer M; Akinsiku, Oladele; Moningka, Natasha C et al. (2012) Sexual dimorphism in development of kidney damage in aging Fischer-344 rats. Gend Med 9:219-31
Behnke, Bradley J; Ramsey, Michael W; Stabley, John N et al. (2012) Effects of aging and exercise training on skeletal muscle blood flow and resistance artery morphology. J Appl Physiol (1985) 113:1699-708
Prisby, Rhonda D; Dominguez 2nd, James M; Muller-Delp, Judy et al. (2012) Aging and estrogen status: a possible endothelium-dependent vascular coupling mechanism in bone remodeling. PLoS One 7:e48564
Muller-Delp, Judy M; Gurovich, Alvaro N; Christou, Demetra D et al. (2012) Redox balance in the aging microcirculation: new friends, new foes, and new clinical directions. Microcirculation 19:19-28
Behnke, Bradley J; Armstrong, Robert B; Delp, Michael D (2011) Adrenergic control of vascular resistance varies in muscles composed of different fiber types: influence of the vascular endothelium. Am J Physiol Regul Integr Comp Physiol 301:R783-90

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