The long-term goal of our laboratory is to define the physiological mechanisms linking muscle blood flow to the metabolic state of the tissue. In response to exercise, skeletal muscle blood flow increases dramatically through a functional vasodilation of the arterioles. We have demonstrated that arachidonic acid metabolites are important in the control of muscle blood flow. The studies in the current proposal will extend these studies and determine the mechanisms by which chronic exercise improves functional vasodilatory in obesity. Obesity is increasing at an alarming rate in the United States and is a major risk factor for a variety of cardiovascular diseases. NIH has initiated clinical trials to determine if exercise training improves cardiovascular health in persons who have both Type 2 diabetes and hypertension, conditions that are prevalent in obesity. Obese humans have an impaired ability to increase muscle blood flow in response to exercise, and the mechanisms underlying this abnormal increase in blood flow (functional hyperemia) are unclear. An impaired functional hyperemia could potentially prevent the obese patient from adequate exercise, a therapy known to improve glucose, lipid and weight control. Therefore, a better understanding of the mechanisms underlying improved functional hyperemia by chronic exercise training in obesity is important. Our recent work has demonstrated that, in obesity, there is an altered arachidonic acid metabolism, resulting in an impaired blood flow response to acute exercise. We have also demonstrated that chronic exercise training improves functional vasodilatory responses in an animal model of obesity. Based on our published and preliminary data the overall goal of this proposal is to test the central hypothesis that chronic exercise training will improve functional vasodilation through improvements in PGI2 vasodilatory responses and decreases in thromboxane vasoconstrictor responses. We propose that these alterations in arachidonic acid metabolism are due to hyperglycemic/hyperlipidemic induced increases in reactive oxygen species. The proposed studies will utilize in vivo and in vitro microcirculatory techniques to provide new and important insights into mechanisms by which chronic exercise training improves functional vasodilatory responses in obesity.

Public Health Relevance

Obesity is increasing at an alarming rate in the United States and is a major risk factor for a variety of cardiovascular diseases. Obese humans have an impaired ability to increase muscle blood flow in response to exercise, which could prevent the obese patient from adequate exercise, a therapy known to improve the elevated glucose, lipids and body weight associated with obesity. Therefore, a better understanding of the mechanisms by which chronic exercise training improves muscle blood flow in obesity is important.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL089581-04
Application #
8223293
Study Section
Hypertension and Microcirculation Study Section (HM)
Program Officer
Ershow, Abby
Project Start
2009-05-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2012
Total Cost
$366,300
Indirect Cost
$118,800
Name
University of Mississippi Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
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