Date of Award
Doctor of Philosophy
Field of Study
Graduate School of Biomedical Sciences
Peter B. Raven
Robert T. Mallet
J. Thomas Cunningham
The arterial baroreflex’s (ABR) operating point (OP) pressure is reset upwards and rightwards from rest in direct relation to the increases in dynamic exercise intensity. However the interneural pathways and signaling mechanisms that lead to upwards and rightwards resetting of the OP pressure, and hence the increases in central sympathetic outflow during exercise, remain to be identified. Data from recent animal investigations have implicated nitric oxide (NO) as a modulator of central sympathetic outflow. For example, introduction of NO centrally dampens sympathetic outflow and there is a growing body of evidence that indicates that central NO is scavenged by centrally generated free radicals (FR), thereby, enabling increased central sympathetic outflow. Furthermore, during dynamic exercise, increases in centrally generated FRs formed by increased intensity-related oxidative metabolism and central angiotensin II (Ang II) production linked to exercise intensity related FR production suggests that FRs are candidate signaling molecules. Whether the primary site of the FRs signaling action occurs within the central nervous system (CNS) or is a result of peripheral chemo- or mechano-receptor input to the CNS remains to be established. Therefore, the aim of the proposed research is to investigate the role of FRs on arterial baroreflex resetting in human subjects.
The first investigation of this project tested the hypothesis that combined central and peripheral FRs play a pivotal role in the exercise related resetting of arterial baroreflex control of arterial blood pressure and muscle sympathetic nerve activity (MSNA) in healthy subjects. The second investigation of this project tested the hypothesis that the Ang II linked FR production-mediated acute ABR-OP pressure resetting during exercise is located within the CNS. From these investigations we identified that: i) free radical production, particularly superoxide, plays a pivotal role in the exercise related rightward and upward resetting of the ABR-OP pressure and the reflex control of central sympathetic outflow; and ii) the major effect of Ang II on ABR-OP pressure resetting and control of central sympathetic outflow occurs centrally.
"The Role of Free Radicals in the Exercise Induced Resetting of the Arterial Baroreflex" Fort Worth, Tx: University of North Texas Health Science Center;