Dose-dependent effect of dobutamine on chemoreflex activity in healthy volunteers.
OBJECTIVE
beta-adrenergic agonists increase peripheral chemoreceptor sensitivity in humans. We tested the hypothesis that beta(1)-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 microg kg(-1) min(-1) (D2.5) and 7.5 microg 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.


CONCLUSIONS
Dobutamine enhances peripheral chemosensitivity at low infusion rates selectively and in a dose-dependent manner. There is a beta(1) adrenoceptor component in dobutamine-evoked increase in peripheral chemosensititivity; however, a contribution of additional adrenoceptor subtypes cannot be excluded.
Pathak
Atul
A
Department of Cardiology, Erasme University Hospital, Université Libre de Bruxelles, Bruxelles, Belgium. pathak@cict.fr
Velez-Roa
Sonia
S
Xhaët
Olivier
O
Najem
Boutaina
B
van de Borne
Philippe
P
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D001262:Atenolol / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000187:drug effects*; D018592:Cross-Over Studies; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood
D000318:Adrenergic beta-Agonists; D004280:Dobutamine; D001262:Atenolol; D010100:Oxygen