Dobutamine potentiates arterial chemoreflex sensitivity in healthy normal humans

Abstract

beta-Adrenergic agonists may increase chemosensitivity in humans. We tested the hypothesis that the beta1-agonist dobutamine increases peripheral chemosensitivity in a double-blind placebo-controlled randomized and crossover study. In 15 healthy subjects, we examined the effects of dobutamine on breathing, hemodynamics, and sympathetic nerve activity (measured using microneurography) during normoxia, isocapnic hypoxia (10% O2), posthypoxic maximal voluntary end-expiratory apnea, hyperoxic hypercapnia, and cold pressor test (CPT). Dobutamine increased ventilation (7.5 +/- 0.3 vs. 6.7 +/- 0.2 l/min, P = 0.0004) during normoxia, markedly enhanced the ventilatory (16.1 +/- 1.6 vs. 11.4 +/- 0.7 l/min, P < 0.0001) and sympathetic (+403 +/- 94 vs. +222 +/- 5%, P < 0.03) responses at the fifth minute of isocapnic hypoxia, and enhanced the sympathetic response to the apnea performed after hypoxia (+501 +/- 107% vs. +291 +/- 38%, P < 0.05). No differences were observed between dobutamine and placebo on the responses to hyperoxic hypercapnia and CPT. Dobutamine increases ventilation during normoxia and potentiates the ventilatory and sympathetic responses to hypoxia in healthy subjects. Dobutamine does not affect the responses to hyperoxic hypercapnia and CPT. We conclude that dobutamine enhances peripheral chemosensitivity.

Effects of β2-adrenergic stimulation on exercise capacity in normal subjects

“…Muscle sympathetic nerve activity (MSNA) was recorded continuously by obtaining multiunit recordings of postganglionic sympathetic activity measured from a nerve fascicle in the peroneal nerve posterior to the Wbular head, as previously described (Velez-Roa et al 2003;Houssiere et al 2006;Beloka et al 2008). Electric activity in the nerve fascicle was measured using tungsten microelectrodes (shaft diameter 200 m, tapering to a non-insulated tip of 1-5 m).…”

“…These include positive chrono-and inotropic eVects (Kiely et al 1995;Hopkins et al 1996) increased chemosensitivity (Yoshiike et al 1995;Velez-Roa et al 2003) increased muscle strength (Martineau et al 1992;Caruso et al 1995) or power (Le Panse et al 2007) and lipolytic and glycolytic actions together with increased metabolic rate (Amoroso et al 1993;Collomp et al 2000;Wong et al 1990) depending on dose and mode of administration.…”

Hyperoxia enhances metaboreflex sensitivity during static exercise in humans

“…This is because hyperoxia suppresses the resting chemoreflex drive in humans (8,26,38). The carotid and aortic chemoreceptors increase MSNA in response to reductions in arterial oxygen content (19,27,42). Short periods of 3-4 min of hyperoxia (38) or hyperoxia with a 50% inspired O 2 fraction (FI O 2 ) (12, 21) do not decrease BP.…”

Effects of digoxin on muscle reflexes in normal humans

“…Sympathetic bursts were identified by careful inspection of the mean voltage neurogram by a single, trained observer blinded to the interventions (Velez-Roa et al 2003). The amplitude of each burst was determined and sympathetic activity was calculated as bursts per minute, multiplied by mean burst amplitude (arbitrary units), and expressed as percent increase from baseline values.…”

“…They were told not to smoke or drink alcohol for the 12 h before the measurements. [MSNA] was recorded continuously by obtaining multiunit recordings of postganglionic sympathetic activity, measured from a nerve fascicle in the peroneal nerve posterior to the fibular head in all subjects, as previously described (Velez-Roa et al 2003). Blood samples were performed from an antecubital vein of the exercising arm at the end of the baseline, the handgrip exercise, and the local circulatory arrest to assess venous plasma potassium and lactate.…”