The cutaneous circulation plays an integral role in human thermoregulation. There are intrinsic age-related changes in the dermal matrix, in the cutaneous vessels, and in autonomic control of blood flow, any or all of which may alter the cutaneous vascular response to local and whole-body thermal stresses. Studies performed under Grant AG07004-01 through -05 demonstrated that during heat stress, the increase in skin blood flow (SkBF) and skin vascular conductance per degree C increment in body core temperature is markedly attenuated in healthy active men and women over the age of 55, when compared to 20-30 year- old subjects. This decrement appears to be due to peripheral rather than central (e.g., hypothalamic) age-related changes. However, many questions remain about aging and control of skin blood flow. The human SkBF response to elevated body temperature is unique in that there is a well developed active sympathetic vasodilator system as well as an adrenergic vasoconstrictor system. Under any given set of environmental influences, the balance between these two competing systems determines the net SkBF, yet it is not known which system is altered by the aging process. The local iontophoresis of bretylium tosylate - which eliminates vasoconstrictor influences, and thus allows for the study of the active vasodilator system in the absence of constrictor effects - provides a tool with which to examine the mechanisms underlying the effects of intrinsic aging on control of SkBF. In addition, interventions aimed at increasing thermally-induced vasodilation in older subjects have not been examined. Therefore, the scope of the proposed continuation of Grant AG- 07004 is to systematically study the effects of age on the control of human skin blood flow, and the mechanisms underlying the age- related changes. Specific research hypotheses are as follows: 1) In vivo maximal SkBF decreases with advancing age; 2) The efferent pathway involved in the attenuated vasodilatory response with aging is the active vasodilator system; 3) The age- related decline in SkBF can be attenuated by exercise training; 3a) The mechanism responsible is enhanced vasodilator system activity at a given core temperature; 4) In post-menopausal women, estrogen (E2) replacement therapy increases SkBF at a given core temperature; a) This response is secondary to an E2- induced isotonic hypervolemia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG007004-07
Application #
2049657
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1987-09-30
Project End
1998-06-30
Budget Start
1995-08-10
Budget End
1996-07-31
Support Year
7
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Organized Research Units
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Greaney, Jody L; Stanhewicz, Anna E; Proctor, David N et al. (2015) Impairments in central cardiovascular function contribute to attenuated reflex vasodilation in aged skin. J Appl Physiol (1985) 119:1411-20
Stanhewicz, Anna E; Alexander, Lacy M; Kenney, W Larry (2015) Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms. Clin Sci (Lond) 129:159-67
Greaney, Jody L; Stanhewicz, Anna E; Kenney, W Larry et al. (2015) Impaired increases in skin sympathetic nerve activity contribute to age-related decrements in reflex cutaneous vasoconstriction. J Physiol 593:2199-211
Greaney, Jody L; Alexander, Lacy M; Kenney, W Larry (2015) Sympathetic control of reflex cutaneous vasoconstriction in human aging. J Appl Physiol (1985) 119:771-82
Greaney, Jody L; Stanhewicz, Anna E; Kenney, W Larry et al. (2014) Lack of limb or sex differences in the cutaneous vascular responses to exogenous norepinephrine. J Appl Physiol (1985) 117:1417-23
Kenney, W Larry; Stanhewicz, Anna E; Bruning, Rebecca S et al. (2014) Blood pressure regulation III: what happens when one system must serve two masters: temperature and pressure regulation? Eur J Appl Physiol 114:467-79
Stanhewicz, Anna E; Greaney, Jody L; Kenney, W Larry et al. (2014) Sex- and limb-specific differences in the nitric oxide-dependent cutaneous vasodilation in response to local heating. Am J Physiol Regul Integr Comp Physiol 307:R914-9
Greaney, Jody L; Stanhewicz, Anna E; Kenney, W Larry et al. (2014) Muscle sympathetic nerve activity during cold stress and isometric exercise in healthy older adults. J Appl Physiol (1985) 117:648-57
Kenney, W Larry; Craighead, Daniel H; Alexander, Lacy M (2014) Heat waves, aging, and human cardiovascular health. Med Sci Sports Exerc 46:1891-9
Bruning, Rebecca S; Dahmus, Jessica D; Kenney, W Larry et al. (2013) Aspirin and clopidogrel alter core temperature and skin blood flow during heat stress. Med Sci Sports Exerc 45:674-82

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