The action of some cholinergic blockers on carotid body chemoreceptors In vivo

Abstract

Chemosensory discharges were recorded in vivo from fine filaments of the carotid nerve containing a few or single active units; their frequency was used as an index of receptor activity. The effects of hemicholinium, atropine, mecamylamine and hexamethonium on the chemosensory discharges elicited by ACh and NaCN were studied in 46 adult cats. Hemicholinium in low concentrations (0.5–1 mg/kg, i.v.) did not change the resting discharge rate or the chemoreceptor response to ACh and NaCN. One-2 h after injections of hemicholinium (2–5 mg/kg, i.v.) the responnse to NaCN was markedly depressed, while that to ACh remained unchanged. Larger doses of the drug (10 mg/kg, i.v.) depressed or blocked the responses to both chemicals. These experiments indicate that transmitter substances (probably ACh) stored in the cells are depleted or decreased by the presence hemicholinium, which blocks ACh synthesis. Atropine in low concentrations (0.2–1 mg/kg, i.v.) depressed the receptor response to ACh without affecting the discharges elicited by NaCN. On the other hand, relatively large doses of the drug (2–10 mg, i.v. and i.a.) blocked or depressed both the basal chemoreceptor discharges and the responses to ACh and NaCN. This depressant effect of atropine on the response to both chemicals lasted for 10–20 min. Mecamylamine (2–10 mg, i.a.) blocked the chemoreceptor response to ACh and NaCN. Naturally occuring chemoreceptor discharges were blocked transiently by the drug. Hexamethonium (2–10 mg, i.a.) was ineffective on the chemoreceptor response to ACh and NaCN in 25% of the chemosensory units examined, and in 50% of them the drug depressed or blocked the ACh-induced response without affecting the NaCN-induced effect. In 25% of the units, both the response to ACh and NaCN was blocked or depressed by the drug. Results indicate the approximate population of nicotinic cholinoceptive sites of chemosensory nerve terminals. It is concluded that a cholinergic mechanism is probably responsible for chemoreceptor impulse initiation. Exogenous ACh appears to be acting on extrasynaptic cholinergic receptors, probably located in the stem of the non-myelinated sensory endings, while natural stimuli and NaCN are probably acting on the glomus cells to liberate ACh, which exerts its effects on synaptic cholinergic sites.