Two powerful reflexes exist capable of mediating the cardiovascular adjustments to(, dynamic exercise; the muscle chemoreflex and the arterial baroreflex. When oxygen delivery to the active skeletal muscles falls below metabolic requirements, metabolites accumulate within the active muscle, stimulating group III and IV afferents which induce an increase in arterial pressure in an attempt to maintain muscle blood flow - termed the muscle chemoreflex. In addition, during dynamic exercise whenever vasodilation in skeletal muscle outstrips cardiac pumping capacities, arterial pressure will fall below the operating point of the baroreflex inducing baroreflex mediated peripheral vasoconstriction and tachycardia. The functional importance of each of these reflexes during dynamic exercise is unclear. Situations exist when these reflexes may be combating each other or when these reflexes may induce cardiovascular responses in the same direction. For example, in patient with peripheral vascular disease, blood flow to active muscle may be restricted inducing muscle chemoreflex mediated increases in arterial pressure. In this setting, the arterial baroreflex would oppose any rise in blood pressure. Alternatively, in patients with cardiac limitations, the exaggerated peripheral vasoconstriction and tachycardia observed during dynamic exercise may stem from activation of the muscle chemoreflex (due to underperfused active skeletal muscle) or via activation of the arterial baroreflex (due to lower than normal arterial pressure) or both. Using two well developed animal models; the conscious dog chronically instrumented to control blood flow to the hindlimb skeletal muscles, and the conscious dog with atrioventricular block in which cardiac output can be controlled on a beat-by-beat basis; this proposal is focused on determining the functional importance of the muscle chemoreflex and ar- terial baroreflex during dynamic exercise. The experiments are designed to activate the muscle chemoreflex and the arterial baroreflex in opposition and concurrently in order to determine the strengths (gains) of each reflex, the efferent mechanisms of action of each reflex, and the extent of interaction between reflexes. A key hypothesis addressed is that the functional importance of each reflex during dynamic exercise is intimately dependent on both the level of cardiac output and the level of dynamic exercise. These studies will provide a firm, quantitative, and mechanistic basis for our understanding of the reflex control of the cardiovascular system during dynamic exercise.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL045038-03
Application #
3473175
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1991-04-01
Project End
1996-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
O'Leary, D S; Robinson, E D; Butler, J L (1997) Is active skeletal muscle functionally vasoconstricted during dynamic exercise in conscious dogs? Am J Physiol 272:R386-91
O'Leary, D S; Rossi, N F; Churchill, P C (1997) Substantial cardiac parasympathetic activity exists during heavy dynamic exercise in dogs. Am J Physiol 273:H2135-40
O'Leary, D S (1996) Heart rate control during exercise by baroreceptors and skeletal muscle afferents. Med Sci Sports Exerc 28:210-7
O'Leary, D S; Woodbury, D J (1996) Role of cardiac output in mediating arterial blood pressure oscillations. Am J Physiol 271:R641-6
Dunbar, J C; O'Leary, D S; Wang, G et al. (1996) Mechanisms mediating insulin-induced hypotension in rats. A role for nitric oxide and autonomic mediators. Acta Diabetol 33:263-8
O'Leary, D S; Sheriff, D D (1995) Is the muscle metaboreflex important in control of blood flow to ischemic active skeletal muscle in dogs? Am J Physiol 268:H980-6
O'Leary, D S; Dunlap, R C; Glover, K W (1994) Role of endothelium-derived relaxing factor in hindlimb reactive and active hyperemia in conscious dogs. Am J Physiol 266:R1213-9
O'Leary, D S (1993) Autonomic mechanisms of muscle metaboreflex control of heart rate. J Appl Physiol 74:1748-54
O'Leary, D S; Seamans, D P (1993) Effect of exercise on autonomic mechanisms of baroreflex control of heart rate. J Appl Physiol 75:2251-7
O'Leary, D S; Rossi, N F; Churchill, P C (1993) Muscle metaboreflex control of vasopressin and renin release. Am J Physiol 264:H1422-7