Interactions between hypoxia, acetylcholine and dopamine in the carotid body of rabbit and cat.
1. Acetylcholine (ACh) and dopamine (DA) were either infused into the carotid artery or applied directly to the surface of the carotid body of twenty-six rabbits and fifteen cats. Afferent discharge of single chemoreceptor units was recorded at a range of Pa,O2 (arterial O2 pressure) values during drug administration. 2. There were no observable systemic effects of either drug when applied to the surface of the carotid body. 3. Acetylcholine tended to depress afferent discharge when applied to the surface of the rabbit carotid body or when infused into the carotid sinus. In the cat, intracarotid and surface application of ACh had mild and inconsistent effects. DA consistently depressed discharge in both species independent of the route of administration. Antagonists of ACh and DA failed to abolish the chemoreceptor response to hypoxia. 4. The changes in afferent discharge elicited by all drugs were small compared with the range of discharge rates attained with physiological stimuli. The effects of ACh and DA were more marked in hyperoxia than in hypoxia for both routes of administration, disappearing at Pa,O2 values close to 20 Torr (7.5 Torr = 1 kPa). 5. A role for DA in the maintenance of the hypoxic response was investigated in six rabbits. After 15 min of hypoxia (Pa,O2 = 21.8 +/- 1.1 Torr; mean +/- S.E.M.) the discharge of single chemoreceptor fibres adapted moderately (to 79.3 +/- 5.2% of maximum discharge). Following administration of domperidone or haloperidol (1.0-5.3 mg kg-1, I.V.) the same fibres responded with equal magnitude to the onset of the hypoxic stimulus but showed a significantly larger adaptation (to 48.5 +/- 4.4%). 6. It is concluded that endogenous ACh and DA are unlikely to mediate the transduction process of the carotid body, but DA may play a role in preventing adaptation to a prolonged hypoxic stimulus.
Ponte
J
J
Department of Anaesthetics, King's College School of Medicine and Dentistry, Denmark Hill, London.
Sadler
C L
CL
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002344:Carotid Body / Q000187:drug effects*; D002415:Cats; D002628:Chemoreceptor Cells / Q000502:physiology; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology; D010100:Oxygen / Q000097:blood*; D011817:Rabbits
D002245:Carbon Dioxide; D004294:Domperidone; D006220:Haloperidol; D000109:Acetylcholine; D010100:Oxygen; D004298:Dopamine