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

• Published in: British journal of clinical pharmacology Vol. 62; no. 3; pp. 272 - 279
• Main Authors: Pathak, Atul, Velez‐Roa, Sonia, Xhaët, Olivier, Najem, Boutaina, Van De Borne, Philippe
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2006; Blackwell Science
• Subjects: Adrenergic beta-Agonists - administration & dosage; Adrenergic beta-Agonists - pharmacology; Adult; Analysis of Variance; Atenolol - pharmacology; Biological and medical sciences; Chemoreceptor Cells - drug effects; chemoreflex; Cross-Over Studies; dobutamine; Dobutamine - administration & dosage; Dobutamine - pharmacology; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Male; Medical sciences; Oxygen - blood; Pharmacodynamics; pharmacology; Pharmacology. Drug treatments; Human; Agonist; Cardiotonic agent; Chemoreflex; β1-Adrenergic receptor; Healthy subject; Dobutamine; β-Adrenergic receptor agonist; Pharmacology; Biological activity; Dose activity relation
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.2006.02657.x

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.