Access Type

Open Access Dissertation

Date of Award

January 2014

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Physiology

First Advisor

Donal S. O'Leary

Abstract

Skeletal muscle ischemia during or immediately following exercise leads to the accumulation of metabolites (e.g., lactate, proton and diprotonated phosphate) which activate chemoreceptive afferents within the muscle leading to a reflex increase in sympathetic outflow generating substantial increases in mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR) - termed the muscle metaboreflex. When the reflex is activated during submaximal dynamic exercise, the pressor response occurs via increased CO with no net peripheral vasoconstriction. When metaboreflex activation is sustained during the recovery from exercise (i.e., post-exercise muscle ischemia - (PEMI)), whereas MAP remains elevated for as long as the ischemia is maintained, HR precipitously declines towards resting levels drawing into question the role of CO in supporting the pressor response. When the reflex increase in CO is attenuated (e.g., in heart failure), heightened peripheral vasoconstriction supports the pressor response. In hypertension (HTN), metaboreflex-mediated increases in ventricular function and CO are markedly attenuated during mild exercise. As sympathetic nerve activity (SNA) is exaggerated in both heart failure and HTN, it is plausible that the mechanisms mediating the attenuation of CO in HTN with muscle metaboreflex activation are similar to those previously described in heart failure. Employing a chronically-instrumented canine model, data were collected from control animals and the same animal after induction of HTN. We addressed three specific questions: 1) what are the mechanism(s) mediating the muscle-metaboreflex-induced pressor response observed during PEMI in normal subjects, 2) what are the mechanism(s) mediating the muscle-metaboreflex-induced pressor response observed during PEMI in hypertensive subjects and 3) does metaboreflex activation during submaximal exercise in hypertensive animals functionally restrain coronary vasodilation further limiting increases in ventricular performance. We found that: 1) the sustained increase in MAP during PEMI is driven by a sustained increase in CO not peripheral vasoconstriction, 2) the attenuated pressor response in HTN is not sustained during PEMI as HR and CO fall to normal recovery levels and 3) in HTN, exaggerated metaborelfex-induced increases in SNA functionally vasoconstrict the coronary vasculature impairing increases in CBF which limits oxygen delivery and ventricular performance.

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