Dopaminergic modulation of respiratory motor output in peripherally chemodenervated goats

J Appl Physiol (1985). 1998 Sep;85(3):946-54. doi: 10.1152/jappl.1998.85.3.946.

Abstract

We examined the ventilatory effects of exogenous dopamine (DA) and norepinephrine (NE) administration in chloralose-anesthetized, paralyzed, artificially ventilated adult goats before and after carotid body denervation (CBD). Intravenous (iv) DA bolus injections and slow iv infusions caused dose-dependent inhibition of phrenic nerve activity (PNA) in carotid body (CB)-intact animals during normoxia and hyperoxia but not during hypercapnia. NE administration in CB-intact goats caused dose-dependent inhibition of PNA of similar magnitude to DA trials. The DA D2-receptor agonists quinelorane and quinpirole inhibited PNA, whereas the DA D1-receptor agonist SKF-81297 had no effect. After CBD, the ventilatory depressant effects of DA persisted, but responses were significantly attenuated compared with CB-intact trials. CBD abolished the inhibitory effect of low-dose NE administration but did not alter ventilatory responses to high-dose NE injection. The peripheral DA D2-receptor antagonist domperidone substantially attenuated the inhibitory effects of DA bolus injections and infusions and reversed the inhibitory ventilatory effect of high-dose DA administration to excitation in some animals. The alpha-adrenoceptor antagonist phentolamine had no effect on DA-induced ventilatory depression. Beta-Adrenoceptor stimulation with isoproterenol produced similar hemodynamic effects to DA administration but had no effect on PNA. We conclude that DA and NE exert both CB-mediated and non-CB-mediated inhibitory effects on respiratory motor output in anesthetized goats. The ventilatory depressant effects that persist in peripherally chemodenervated animals are DA D2-receptor mediated, but their exact location remains speculative.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Carotid Body / physiology
  • Dopamine / pharmacology
  • Dopamine / physiology*
  • Dopamine Agonists / pharmacology
  • Female
  • Goats
  • Hemodynamics / physiology
  • Hypercapnia / physiopathology
  • Male
  • Muscle Denervation
  • Peripheral Nervous System / physiology*
  • Phentolamine / pharmacology
  • Respiratory Mechanics / physiology
  • Respiratory Muscles / physiology*

Substances

  • Adrenergic alpha-Antagonists
  • Dopamine Agonists
  • Dopamine
  • Phentolamine