Dopaminergic modulation of respiratory motor output in peripherally chemodenervated goats.
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.
O'Halloran
K D
KD
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA. kenoh@svm.vetmed.wisc.edu
Janssen
P L
PL
Bisgard
G E
GE
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002344:Carotid Body / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D006041:Goats; D006439:Hemodynamics / Q000502:physiology; D006935:Hypercapnia / Q000503:physiopathology; D008297:Male; D009121:Muscle Denervation; D017933:Peripheral Nervous System / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D015656:Respiratory Mechanics / Q000502:physiology; D012132:Respiratory Muscles / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D018491:Dopamine Agonists; D004298:Dopamine; D010646:Phentolamine