Regulation of sympathetic vasoconstriction in resting and contracting skeletal muscle

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The precise regulation of blood pressure and the distribution of blood flow are essential to ensure that vital organs and tissues receive an adequate supply of oxygen and other nutrients to sustain life. Blood pressure and tissue blood flow are controlled by carefully regulating resistance in arteries. Neural activity in the sympathetic nervous system leads to the release of chemical (neurotransmitters) that constrict peripheral blood vessels and increase arterial resistance. Therefore, the sympathetic nervous system is an important regulator of blood pressure, tissue blood flow and vascular function. The long-term objective of my research program is to establish a mechanistic understanding of sympathetic nervous system regulation of blood pressure and skeletal muscle blood flow at rest, during exercise and in response to physiological stress. I am also interested in understanding whether sympathetic nervous system control of the cardiovascular system can be enhanced. I aim to identify potential therapeutic targets and specific interventions that will produce adaptations and elucidate specific mechanisms responsible for the adaptations. My laboratory uses an integrative physiology experimental approach in combination with pharmacology and molecular techniques to investigate mechanisms that regulate sympathetic neurovascular control and plasticity from the cellular to the integrated systems level. The short-term objectives in this grant will investigate the role of pannexin-1 (Panx1) channels in a-adrenergic receptor mediated vasoconstriction and whether sex and exercise training modulate Panx1 function (Objective 1). Objectives 2-4 will investigate whether vanilloid-type transient receptor potential ion channels (Objective 2), cytochrome P450 enzymes (Objective 3) and adenosine triphosphate (Objective 4) alter sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle of sedentary and exercise trained males and females. Importantly, each objective includes a carefully designed exercise training intervention and sex-based analysis. This research will advance our understanding of the important physiological mechanisms involved in sympathetic nervous system control of the cardiovascular system. The research may also have important biomedical implications with respect to the control of blood pressure and the perfusion of vital organs and tissues at rest and in response to physiological stress (e.g. acute and chronic exercise). The proposed studies utilize an array of cutting edge experimental techniques and an integrative scientific approach which provides a rich training environment. I will continue to engage undergraduate and graduate students in my research, and thus, the research will contribute to the development of the next generation of scientific personnel and future research innovation and excellence in Canada.