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(Circulation Research. 2007;100:1371.)
© 2007 American Heart Association, Inc.

Integrative Physiology

Carotid Chemoreceptor Modulation of Regional Blood Flow Distribution During Exercise in Health and Chronic Heart Failure

Michael K. Stickland, Jordan D. Miller, Curtis A. Smith, Jerome A. Dempsey

From The John Rankin Laboratory of Pulmonary Medicine, University of Wisconsin, Madison.

Correspondence to Michael Stickland, PhD, Assistant Professor, Division of Pulmonary Medicine, Department of Medicine, 2E4.42 Walter C. Mackenzie, Health Sciences Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2B7. E-mail Michael.Stickland{at}ualberta.ca

Previous work has shown sensitization of carotid chemoreceptor (CC) responsiveness during exercise as well as in chronic heart failure (CHF). Accordingly, we hypothesized that the CCs contribute to the sympathetic restraint of skeletal muscle blood flow during exercise and CHF. We examined the effect of transient CC inhibition on total (Con_T) and hindlimb (Con_L) conductance, and blood pressure at rest and during exercise (2.5 miles per hour, 5% grade) in chronically instrumented dogs. Via a carotid arterial catheter, CCs were inhibited using dopamine (5 to 10 µg/kg) or hyperoxic lactated Ringer’s solution. Although vasodilation did not occur with CC inhibition in resting healthy dogs, CC inhibition during exercise caused an immediate vasodilatory response (increase in Con_T and Con_L and decrease in blood pressure). When comparing the peak Con_L response from CC inhibition versus -adrenergic blockade (phentolamine), we found that the CCs accounted for approximately one-third of the total sympathetic restraint during exercise. CHF was then induced by chronic rapid cardiac pacing and characterized by impaired cardiac function, enhanced chemosensitivity, and greater sympathetic restraint at rest and during exercise. In contrast to healthy dogs, CC inhibition in resting CHF dogs produced vasodilation, whereas a similar vasodilatory response was observed during exercise in CHF as compared with healthy dogs. The vasodilation following CC inhibition during exercise and in CHF was abolished with -adrenergic blockade and was absent in healthy exercising animals after carotid body denervation. These results establish an important role for the CCs in cardiovascular control in the healthy animal during exercise and in the CHF animal both at rest and during exercise.

Key Words: chemosensitivity • sympathetic nervous activity • exercise • chronic heart failure • blood flow

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