Perfusion of Active Muscles: Metabolites and Nerves

Project: Research project

Project Details


DESCRIPTION (provided by applicant): The overall goal of this research program is to continue to investigate how the autonomic nervous system and factors produced by contracting muscles interact to regulate muscle blood flow in humans. This proposal seeks to test the general hypothesis that nitric oxide (NO) limits adrenergic receptor-mediated vasoconstriction in contracting human skeletal muscles. The concept is that locally produced NO blunts sympathetic vasoconstriction in the active muscles as a part of a phenomenon termed "functional sympatholysis." To test our hypothesis we will address the following specific aims: (1) we will determine the impact of exercise on postsynaptic alpha1 and cx2 adrenergic receptor-mediated vasoconstriction in human skeletal muscles; we hypothesize that exercise will blunt post-synaptic a2-mediated vasoconstriction in contracting human skeletal muscle and that a1-mediated constriction will be unaffected; (2) we will determine if locally-produced NO is responsible for the blunting of sympathetic constriction in active human muscles; we hypothesize that NO limits post-synaptic a2 (but not alpha1) receptor mediated vasoconstriction in contracting human skeletal muscle; (3) we will determine if normal aging is associated preserved sympathetic vasoconstriction in the active muscles; we hypothesize that healthy older subjects will be relatively resistant to functional sympatholysis and demonstrate substantial sympathetic vasoconstriction in their exercising muscles. Our hypotheses and techniques are a logical extension of the last ten years of HL-46493, which has focused on sympathetic control of blood flow to contracting muscles and the role of NO in physiological vasodilation. Based on this experience we believe that we have proposed innovative and interpretable studies that will provide significant new information on functional sympatholysis in humans. In addition to providing insight about how sympathetic nerves regulate blood flow to contracting muscles, these studies are also likely to yield fundamental information on how adrenergic vasoconstrictor responses are altered when there is concurrent vasodilation.
Effective start/end date1/17/9211/30/12


  • Medicine(all)