Dose-dependent effect of dobutamine on chemoreflex activity in healthy volunteers

Aims  β-adrenergic agonists increase peripheral chemoreceptor sensitivity in humans. We tested the hypothesis that β₁-agonist-related increase in peripheral chemoreflex sensitivity is selective and dose-dependent.

Methods  Using a double-blind, placebo-controlled, randomized, crossover study, we examined the effects of dobutamine (n = 17 healthy subjects) at perfusion rates of 2.5 µg kg⁻¹ min⁻¹ (D2.5) and 7.5 µg kg⁻¹ min⁻¹ (D7.5) on ventilation, haemodynamics and sympathetic nerve activity during normoxia, isocapnic hypoxia, posthypoxic maximal voluntary end-expiratory apnoea, hyperoxic hypercapnia and cold pressor test (CPT). We analysed the effect of pretreatment with atenolol on dobutamine-evoked chemosensitivity.

Results  Dobutamine dose-dependently increased ventilation (placebo 6.7 ± 0.5 vs. D2.5 7.8 ± 0.4 vs. D7.5 8.7 ± 0.4 l min⁻¹, P < 0.005) during normoxia, enhanced the ventilatory (placebo 14.4 ± 0.6 vs. D2.5 17.3 ± 0.8 vs. D7.5 22.5 ± 1.9 l min⁻¹, P < 0.0001) and sympathetic (placebo + 215 ± 31 vs. D2.5 + 285 ± 19 vs. D7.5 + 395 ± 50% of baseline, P < 0.03) responses at the fifth minute of isocapnic hypoxia and enhanced the sympathetic response to apnoea performed after hypoxia (increase after 5 min of hypoxia: + 290 ± 43% for placebo vs.+ 360 ± 21% for D2.5 vs. 537 ± 69% for D7.5, P < 0.05). No differences were observed between dobutamine and placebo in the responses to hyperoxic hypercapnia and CPT. Atenolol inhibited the dobutamine-related hyperventilation and apnoea shortening during normoxia and hypoxia.

Conclusion  Dobutamine enhances peripheral chemosensitivity at low infusion rates selectively and in a dose-dependent manner. There is a β₁ adrenoceptor component in dobutamine-evoked increase in peripheral chemosensititivity; however, a contribution of additional adrenoceptor subtypes cannot be excluded.