The mechanisms responsible for the redistribution of blood flow during exercise are not well understood. Previous investigations in both animals and humans have shown that reductions in blood flow to exercising skeletal muscle elicit a neural reflex (termed the muscle chemoreflex) which produces an augmented blood pressure response to exercise. The increased blood pressure partially restores blood flow to the ischemic muscle. The effects of activation of the muscle chemoreflex on vasomotor tone in other vascular beds, interaction with other autonomic reflexes, the specific stimuli eliciting the reflex, and the central pathways of the reflex are not known. This proposal outlines experiments designed to more fully characterize the effects and mechanism of activation of the muscle chemoreflex in conscious animals during dynamic exercise.
The specific aims of this research project are:
Aim 1. To determine the effect of the muscle chemoreflex on vascular conductance in a visceral organ (kidney).
Aim 2. To determine the effect of the muscle chemoreflex on vascular conductance in nonischemic exercising and nonexercising forelimb muscle.
Aim 3. To determine if there is a difference between the threshold for changes in renal vascular conductance and that for changes in forelimb vascular conductance.
Aim 4. To determine if there is an interaction between the muscle chemoreflex and reflexes arising from cardiac receptors.
Aim 5. To determine the degree to which the arterial baroreflexes oppose the muscle chemoreflex-induced alterations in vascular conductance of the kidneys and nonischemic exercising skeletal muscle.
Aim 6. To determine the effect of the muscle chemoreflex on ventilation.
Aim 7. To determine the role of lactic acid in activating the muscle chemoreflex.
Aim 8. To determine the role of the C1 area of the rostral ventrolateral medulla in mediating the muscle chemoreflex. The results of the proposed studies will yield important new information regarding the basic mechanisms underlying the cardiovascular responses to dynamic exercise and the role of chemically sensitive receptors in mediating those responses. Additionally, the results may provide some valuable insights into the pathophysiology of peripheral vascular disease. As a result of reductions in blood flow to exercising muscle, patients with peripheral vascular disease exhibit elevated blood pressures and lactate concentrations during exercise. The proposed experimental model simulates the pathological consequences of this disease.
