Experiments of this proposal will examine how exercise training affects regulation of nitric oxide in coronary collaterals developed in response to chronic coronary occlusion in miniature swine.
Five specific aims are proposed to systematically evaluate the effects of chronic exercise on various cellular biochemical events necessary for nitric oxide production: 1) Regulation of nitric oxide by changes in intracellular calcium will be examined; 2) the synergism between angiogenic growth factors, vascular endothelial growth factor (VEGF), and basic fibroblast growth factors (bFGF) and endothelial function will be examined; 3) regulation of superoxide dismutase will be evaluated to determine how production of superoxide radicals may relate to the bioavailability or stability of nitric oxide; 4) regulation of plasmalemmal caveolae microdomains will be examined; 5) these various aspects of control of nitric oxide (Specific Aims 1-4) will be compared between vessels derived from male and female animals. Results of these experiments will identify underlying endothelial mechanisms and sites of action which may implicate potential new therapeutic directions for optimizing blood flow to collateral-dependent myocardium distal to a chronic coronary artery occlusion in patients with coronary artery disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064931-04
Application #
6561410
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Liang, Isabella Y
Project Start
2000-07-03
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
4
Fiscal Year
2002
Total Cost
$360,000
Indirect Cost
Name
Texas A&M University
Department
Physiology
Type
Schools of Medicine
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845
Zheng, Xiaoxu; Heaps, Cristine L; Fisher, Steven A (2015) Myosin phosphatase isoforms and related transcripts in the pig coronary circulation and effects of exercise and chronic occlusion. Microvasc Res 98:166-71
Dongaonkar, R M; Nguyen, T L; Quick, C M et al. (2015) Mesenteric lymphatic vessels adapt to mesenteric venous hypertension by becoming weaker pumps. Am J Physiol Regul Integr Comp Physiol 308:R391-9
Robles, Juan Carlos; Heaps, Cristine L (2015) Adaptations of the endothelin system after exercise training in a porcine model of ischemic heart disease. Microcirculation 22:68-78
Heaps, Cristine L; Robles, Juan Carlos; Sarin, Vandana et al. (2014) Exercise training-induced adaptations in mediators of sustained endothelium-dependent coronary artery relaxation in a porcine model of ischemic heart disease. Microcirculation 21:388-400
Xie, Wei; Parker, Janet L; Heaps, Cristine L (2013) Exercise training-enhanced, endothelium-dependent dilation mediated by altered regulation of BK(Ca) channels in collateral-dependent porcine coronary arterioles. Microcirculation 20:170-82
Deer, Rachel R; Heaps, Cristine L (2013) Exercise training enhances multiple mechanisms of relaxation in coronary arteries from ischemic hearts. Am J Physiol Heart Circ Physiol 305:H1321-31
Xie, Wei; Parker, Janet L; Heaps, Cristine L (2012) Effect of exercise training on nitric oxide and superoxide/H?O? signaling pathways in collateral-dependent porcine coronary arterioles. J Appl Physiol (1985) 112:1546-55
Robles, Juan Carlos; Sturek, Michael; Parker, Janet L et al. (2011) Ca2+ sensitization and PKC contribute to exercise training-enhanced contractility in porcine collateral-dependent coronary arteries. Am J Physiol Heart Circ Physiol 300:H1201-9
Sarin, Vandana; Muthuchamy, Mariappan; Heaps, Cristine L (2011) Ca²? sensitization of cardiac myofilament proteins contributes to exercise training-enhanced myocardial function in a porcine model of chronic occlusion. Am J Physiol Heart Circ Physiol 301:H1579-87
Heaps, Cristine L; Parker, Janet L (2011) Effects of exercise training on coronary collateralization and control of collateral resistance. J Appl Physiol (1985) 111:587-98

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