Date of Award

2016

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy in Biological Sciences (PhD)

Administrative Home Department

Department of Biological Sciences

Advisor 1

Jason R. Carter

Committee Member 1

Qinghui Chen

Committee Member 2

Zhiying Shan

Committee Member 3

Shane Mueller

Abstract

One in three Americans suffers from hypertension, and another 1/3 are diagnosed as prehypertensive, according to the latest heart and stroke statistics. The sympathetic nervous system, widely recognized as a key regulator of blood pressure, is believed to be overactive in hypertensive patients. Muscle sympathetic nerve activity (MSNA) response to laboratory stressors, such as mental stress, have been extensively used in human experiments to study the sympathetic outflow of individuals with an increased risk of developing high blood pressure later in life. Family history of hypertension (FHH) and race are two widely known risk factors for essential hypertension, but the physiological mechanisms underlying these relations are not clearly elucidated. Although mental stress consistently increases arterial blood pressure, it is often associated with a highly variable MSNA responsiveness between individuals. Therefore, we conducted three studies to investigate the reliability of MSNA measures and the role of FHH and race on the sympathetic reactivity to mental stress. In Study 1, we examined MSNA reactivity to mental stress across three experimental sessions. Sixteen men and women (age 21±1 years) performed two experimental sessions within a single laboratory visit and a third experimental session one month later. Each experimental session consisted of a mental stress trial via mental arithmetic and a cold pressor test (CPT) trial. The consistencies of blood pressure (BP), heart rate (HR) and MSNA reactivity were measured, and were determined using the intraclass correlation coefficient. In Study 2, we analyzed BP and MSNA responsiveness to mental stress in a large and generalizable cohort of young adults with and without FHH. We hypothesized that subjects with FHH would demonstrate greater sympathoexcitation to mental stress than subjects without FHH. A total of 87 subjects (55 men, 32 women; 18-40 years) from recently published (n=45) and ongoing (n=42) studies were examined. 57 subjects had complete MSNA recordings at baseline (19 with FHH, 38 without FHH). In Study 3, we compared muscle sympathetic nerve activity (MSNA) responses to mental stress in a group of young black and NHW participants. We hypothesized that the sympathoexcitation associated with mental stress would be greater in black adults compared to NHW. Thirty-five male adults (19 black, 23±1 years; 16 NHW, 22±1 years) were examined during a 5 min supine baseline and 5 min of mental stress (via mental arithmetic). Neural and cardiovascular measurements for these studies included blood pressure (sphygmomanometer and beat-to-beat finger plethysomography), HR (via electrocardiogram), and MSNA (via microneurography) during five min of supine rest and five min of mental stress (via mental arithmetic). The results of these investigations demonstrate the stability of the sympathetic neural reactivity to mental stress and, more importantly, reveal the impact of heredity and race on that reactivity. These novel findings provide new and valuable mechanistic insight regarding the complex and poorly understood relations among mental stress, sympathetic nervous system and risk of cardiovascular disease.

Available for download on Monday, June 05, 2017

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