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Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706
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
-adrenoceptor antagonist phentolamine had no effect on DA-induced
ventilatory depression.
-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.
dopamine; norepinephrine; domperidone; carotid body; phrenic nerve
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