The purpose of this research program is to understand vascular adaptation within skeletal muscle in response to acute and chronic exposure to exercise. We have shown that exercise training produces an increase in the capacity of skeletal muscle vascular beds to transport nutrients to the muscle. The data suggest that this increase is most evident in the muscle tissue with the greatest relative increase in activity during the training bouts. The experiments will test the hypothesis that training induced angiogenesis occurs specifically in and around the muscle fibers that are required to have the largest increase in activity during the training bouts and that intense endurance training results in increased endurance to prolonged exercise due to these changes in the skeletal muscle vasculature combined with increases in maximal cardiac output. We will also test the hypothesis that these adaptations occur in all mammals by determining if similar vascular adaptations are seen in trained miniature swine. Finally, the study of the mechanisms responsible for skeletal muscle exercise hyperemia will be continued. Experiments will be conducted to determine the role of the """"""""muscle pump"""""""" mechanism in muscle perfusion during exercise. Skeletal muscle vascular function will continue to be assessed with measurements of total and regional blood flows, capillary permeability surface-area products, capillary filtration coefficients, capillary protein osmotic reflection coefficients, isogravimetric capillary pressures, total resistance, pre- and post-capillary resistances and standard hemodynamics. Whole body oxygen consumption, arterial and venous blood gases and lactates will be measured in miniature swine during exercise and biochemical, anatomical and morphometric indexes of training induced adaptations in skeletal muscle will also be obtained to elucidate the interactions of exercise, oxygen transport systems, and skeletal muscle biochemistry. These studies will reveal adaptive mechanisms involved in and among oxygen transport systems (central and peripheral) and skeletal muscle oxidative biochemical pathways in response to acute and chronic increases in metabolic demand.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL036088-03A2
Application #
3350716
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1985-09-01
Project End
1993-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Schools of Veterinary Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Padilla, Jaume; Thorne, Pamela K; Martin, Jeffrey S et al. (2017) Transcriptomic effects of metformin in skeletal muscle arteries of obese insulin-resistant rats. Exp Biol Med (Maywood) 242:617-624
Linden, Melissa A; Fletcher, Justin A; Meers, Grace M et al. (2016) A return to ad libitum feeding following caloric restriction promotes hepatic steatosis in hyperphagic OLETF rats. Am J Physiol Gastrointest Liver Physiol 311:G387-95
Linden, Melissa A; Sheldon, Ryan D; Meers, Grace M et al. (2016) Aerobic exercise training in the treatment of non-alcoholic fatty liver disease related fibrosis. J Physiol 594:5271-84
Olver, T Dylan; Laughlin, M Harold (2016) Endurance, interval sprint, and resistance exercise training: impact on microvascular dysfunction in type 2 diabetes. Am J Physiol Heart Circ Physiol 310:H337-50
Laughlin, M Harold (2016) Physical activity-induced remodeling of vasculature in skeletal muscle: role in treatment of type 2 diabetes. J Appl Physiol (1985) 120:1-16
Bender, Shawn B; Laughlin, M Harold (2015) Modulation of endothelial cell phenotype by physical activity: impact on obesity-related endothelial dysfunction. Am J Physiol Heart Circ Physiol 309:H1-8
Linden, Melissa A; Lopez, Kristi T; Fletcher, Justin A et al. (2015) Combining metformin therapy with caloric restriction for the management of type 2 diabetes and nonalcoholic fatty liver disease in obese rats. Appl Physiol Nutr Metab 40:1038-47
Laughlin, M Harold; Padilla, Jaume; Jenkins, Nathan T et al. (2015) Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats. J Appl Physiol (1985) 119:583-603
Linden, Melissa A; Fletcher, Justin A; Morris, E Matthew et al. (2015) Treating NAFLD in OLETF rats with vigorous-intensity interval exercise training. Med Sci Sports Exerc 47:556-67
Laughlin, M Harold; Padilla, Jaume; Jenkins, Nathan T et al. (2015) Exercise training causes differential changes in gene expression in diaphragm arteries and 2A arterioles of obese rats. J Appl Physiol (1985) 119:604-16

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