DOPAMINERGIC MODULATION OF RESPIRATORY MOTOR OUTPUT IN PERIPHERALLY CHEMODENERVATED GOATS

We examined the ventilatory effects of exogenous dopamine (DA) and nor epinephrine (NE) administration in chloralose-anesthetized, paralyzed, artificially ventilated adult goats before and after carotid body den ervation (CBD). Intravenous (iv) DA bolus injections and slow iv infus ions 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 do se-dependent inhibition of PNA of similar magnitude to DA trials. The DA D-2-receptor agonists quinelorane and quinpirole inhibited PNA, whe reas the DA D-1-receptor agonist SKF-81297 had no effect. After CBD, t he 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 alte r ventilatory responses to high-dose NE injection. The peripheral DA: D-2-receptor antagonist domperidone substantially attenuated the inhib itory effects of DA bolus injections and infusions and reversed the in hibitory ventilatory effect of high-dose DA administration to excitati on in some animals. The alpha-adrenoceptor antagonist phentolamine had no effect on DA-induced ventilatory depression. beta-Adrenoceptor sti mulation with isoproterenol produced similar hemodynamic effects to DA administration but had no effect on PNA. We conclude that DA and NE e xert both CB-mediated and non-CB-mediated inhibitory effects on respir atory motor output in anesthetized goats. The ventilatory depressant e ffects that persist in peripherally chemodenervated animals are DA D-2 -receptor mediated, but their exact location remains speculative.