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Access Type

WSU Access

Date of Award

January 2017

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Pharmacology

First Advisor

Patrick J. Mueller

Second Advisor

Nicholas Davis

Abstract

A sedentary lifestyle is a major risk factor for the development of cardiovascular disease (CVD), the leading cause of death among Americans. Increasing evidence implicates increased sympathetic nerve activity (SNA) as the link between a sedentary lifestyle and CVD. The research presented in this dissertation examines the region of the brainstem known as the rostral ventrolateral medulla (RVLM) and how its regulation of SNA changes as a result of sedentary conditions. Our group has previously reported that sedentary conditions enhance splanchnic SNA in response to pharmacologically induced decreases in blood pressure or by direct activation of the RVLM via microinjection of the amino acid glutamate. More recently, our group has published the first evidence of overt structural differences in phenotypically identified RVLM neurons from sedentary versus physically active rats. Although collectively these studies suggest that a sedentary lifestyle results in increased activity and sensitivity of presympathetic RVLM neurons involved in blood pressure regulation, direct evidence of this proposed mechanism for the observed increased splanchnic SNA is lacking. The studies presented in this dissertation use in vivo characterization and juxtacellular labeling of RVLM neurons to examine the potential mechanistic connection and physiological relevance of overt changes in their structure and function and how they relate to enhanced SNA in sedentary versus physically active rats. These cross sectional studies are complemented by longitudinally based studies of in vivo neuronal activity in the RVLM utilizing manganese-enhanced magnetic resonance imaging (MEMRI). The information gained from these studies will contribute to our understanding of how a sedentary lifestyle contributes to the development of CVD and may provide information on new therapeutic targets in the brain to prevent or slow the progression of CVD.

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