Intracarotid norepinephrine infusions inhibit ventilation in goats.
Plasma norepinephrine (NE) increases from rest to exercise during normoxic exercise, and significantly more during hypoxic exercise in goats. To determine carotid body (CB) mediated effects of increased NE on ventilatory control, we investigated ventilatory responses to intracarotid NE infusions in awake, resting goats. NE was infused (0.5-5.0 micrograms.kg-1 x min-1, 2-3 min) into either a CB intact or contralateral CB-denervated carotid artery in both normoxia and hypoxia (FIO2. = 0.11). PRE-infusion measurements of arterial blood gases, blood pressure and pulmonary ventilation (VI) were compared with values 30-45 sec after beginning NE infusions at 1.0 micrograms.kg-1 x min-1. On the CB-intact side, NE infusions decreased VI by an average of 43% (P < 0.05) and increased PaCO2 4.0 +/- 0.3 mmHg (P < 0.05); ventilatory inhibition preceded an increase in arterial blood pressure. NE infusions on the CB-denervated side had no significant effects on VI or PaCO2, but still increased blood pressure to the same level as infusions on the CB-intact side. In hypoxia, NE infusions on the intact side no longer inhibited VI. NE induced VI inhibition in normoxia was similar in magnitude and time course to dopamine induced VI inhibition. Experiments were repeated following administration the alpha-adrenergic receptor antagonist, phenoxybenzamine (1 mg.kg-1, i.v.) the beta-adrenergic receptor antagonist, propranolol (1 mg.kg-1, i.v.) and the D2-dopamine receptor antagonist, domperidone (1 mg.kg-1, i.v.). Phenoxybenzamine partially blocked NE induced ventilatory depression and domperidone blocked it, but propranolol had no effect. These data indicate that NE inhibits ventilation in goats via effects on carotid chemoreceptors. NE induced inhibition is independent of changes in blood pressure or baroreceptor feedback, and appears to involve both alpha-adrenergic and D2-dopaminergic receptors.
Pizarro
J
J
Department of Comparative Biosciences, University of Wisconsin, Madison 53706.
Warner
M M
MM
Ryan
M
M
Mitchell
G S
GS
Bisgard
G E
GE
D000818:Animals; D002339:Carotid Arteries; D002344:Carotid Body / Q000502:physiology*; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D006041:Goats / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology; D007269:Injections, Intra-Arterial; D009638:Norepinephrine / Q000008:administration & dosage*; D010643:Phenoxybenzamine / Q000494:pharmacology; D012016:Reference Values; D012119:Respiration / Q000187:drug effects*
D010643:Phenoxybenzamine; D004294:Domperidone; D004298:Dopamine; D009638:Norepinephrine