The candidate's short-term goal is to obtain advanced research training to significantly expand his research capabilities. The long-term goal of the candidate is to determine the mechanisms underlying detrimental age-associated changes in neurocirculatory control in humans. The candidate has an established ability and commitment to performing biomedically significant aging research and has successfully obtained extramural funding (Individual NRSA). Members of the mentoring team have a strong history of performing high quality extramurally-supported aging research and of training investigators. The resources at the Penn State College of Medicine (host institution) are excellent. The research training plan involves aspects critical to the development of future independent investigators such as formal classwork training, training in the use of modern experimental techniques, presenting and disseminating research findings, direct mentoring, and interacting with established investigators. Studies outlined in this proposal will utilize direct recordings of arm and leg muscle sympathetic nerve activity (MSNA), interstitial norepinephrine concentrations [NE]i in skeletal muscle, and limb blood flow to integratively examine mechanisms underlying age- and limb-related differences in peripheral blood flow regulation during central hypovolemic stress in humans. The following hypotheses will be tested: 1) resting and central hypovolemia-induced increases in MSNA are similar in the arm and leg of older adults. However, increases in limb MSNA during central hypovolemia elicit blunted vasoconstrictor responses in both the arm and leg of older compared to younger adults. 2) [NE]i is greater in the arm than the leg at rest and during central hypovolemia in young adults. Moreover, both arm and leg [NE]i are greater in older adults at rest and during central hypovolemia compared to young adults. 3) The mechanisms underlying age- and limb-related differences in [NE]i involve modulators of synaptic norepinephrine levels (uptake 1), but not presynaptic alpha-2 adrenergic modulation of NE release.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AG024420-02
Application #
7250191
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Chen, Wen G
Project Start
2006-07-01
Project End
2011-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$110,592
Indirect Cost
Name
Pennsylvania State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Clark, Christine M; Monahan, Kevin D; Drew, Rachel C (2018) Omega-3 polyunsaturated fatty acid supplementation reduces blood pressure but not renal vasoconstrictor response to orthostatic stress in healthy older adults. Physiol Rep 6:e13674
Clark, Christine M; Monahan, Kevin D; Drew, Rachel C (2016) Omega-3 polyunsaturated fatty acid supplementation attenuates blood pressure increase at onset of isometric handgrip exercise in healthy young and older humans. Physiol Rep 4:
Clark, Christine M; Monahan, Kevin D; Drew, Rachel C (2015) Aging augments renal vasoconstrictor response to orthostatic stress in humans. Am J Physiol Regul Integr Comp Physiol 309:R1474-8
Wilson, Thad E; Klabunde, Richard E; Monahan, Kevin D (2014) Using thermal stress to model aspects of disease states. J Therm Biol 43:24-32
Solaiman, Adil Z; Feehan, Robert P; Chabitnoy, Amy M et al. (2014) Ventilatory responses to chemoreflex stimulation are not enhanced by angiotensin II in healthy humans. Auton Neurosci 183:72-9
Monahan, Kevin D; Feehan, Robert P; Sinoway, Lawrence I et al. (2013) Contribution of sympathetic activation to coronary vasodilatation during the cold pressor test in healthy men: effect of ageing. J Physiol 591:2937-47
Gao, Zhaohui; Wilson, Thad E; Drew, Rachel C et al. (2012) Altered coronary vascular control during cold stress in healthy older adults. Am J Physiol Heart Circ Physiol 302:H312-8
Snyder, K A M; Shamimi-Noori, S; Wilson, T E et al. (2012) Age- and limb-related differences in the vasoconstrictor response to limb dependency are not mediated by a sympathetic mechanism in humans. Acta Physiol (Oxf) 205:372-80
Sielatycki, John A; Shamimi-Noori, Saum; Pfeiffer, Michael P et al. (2011) Adrenergic mechanisms do not contribute to age-related decreases in calf venous compliance. J Appl Physiol 110:29-34
Wilson, Thad E; Monahan, Kevin D; Fogelman, Amy et al. (2010) Aerobic training improves in vivo cholinergic responsiveness but not sensitivity of eccrine sweat glands. J Invest Dermatol 130:2328-30

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