Our long-term objective is understanding the role of vascular adaptations in alterations of skeletal muscle phenotype induced by exercise training (EX). EX produces changes in vascular structure and control of blood flow in skeletal muscle.
Aim 1 will determine the distribution of increased endothelium-dependent dilation (EDD) and altered endothelial phenotype (expression of eNOS and other endothelial genes) as well as whether EX alters vasomotor responsiveness of smooth muscle (VSM) to stretch and/or constrictor agents in skeletal muscle arteries. Vasomotor responsiveness and EDD will be examined in vitro in isolated arteries and arterioles (1A - 4A). Because results suggest that adaptive mechanisms are not the same in vascular beds of different muscle phenotypes and along the arterial tree in a muscle, Aim 2 will assess changes of endothelial phenotype in muscle arteries/arterioles using immunoblots, immunohistochemistry, and RT-PCR to test the following hypotheses: 1) eNOS expression increases with decreasing diameter along the arteriolar tree; 2) Endurance EX increases eNOS content selectively in arterioles of FOG muscle; 3) In contrast, interval sprint training increases eNOS selectively in arterioles of FG muscle; 4) Shear stress and 5) Transmural stretch increase eNOS transcription; and 6) Stretch and shear stress interact in control of eNOS transcription. Application of molecular techniques and concepts will establish mechanisms for differences in endothelial and VSM phenotypes along the arterial tree and for Exinduced changes in the phenotype of these vascular cells.
Aim 3 will test the hypotheses that EX-induced increases in BF capacity result from increases inarteriolar number and/or size and that EX-induced artedogenesls by arterialization of capillaries and will determine the role of NO as a signal for adaptation. Mathematical modeling of data will determine the relative importance of structural remodeling of artedolar networks versus changes in control of vascular resistance in EX-induced increases in BF capacity. The experimental designs allow integration of knowledge of muscle fiber type composition, recruitment patterns during training bouts, EX-induced changes in skeletal muscle phenotype, and vascular anatomy. This will provide improved understanding of fundamental I processes in co-adaptation of skeletal muscle phenotype and arterial trees. Understanding these mechanisms I is important because there is a growing body of evidence that EX-induced changes in vascular structure/function may counter-act the vascular effects of peripheral artery disease, heart failure, diabetes, and hypertension. ? ? ?
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