Acetylcholine and carotid body excitation during hypoxia in the cat

The purpose of this study was to test the hypothesis that acetylcholine (ACh) is an excitatory neurotransmitter during the hypoxic stimulation of the carotid body. Cats were anesthetized, paralyzed, and artificially ventilated. The common carotid artery was fitted with a loop containing a stopcock for selectively perfusing the carotid body. Neural activity was recorded from the whole carotid sinus nerve. After the cats had been ventilated on 10% O2 for 3 min with the carotid body being normally perfused with its own hypoxic arterial blood, the stopcock was turned, and either equally hypoxic Krebs-Ringer bicarbonate solution (KRB) containing alpha-bungarotoxin, mecamylamine, and atropine or hypoxic blocker-free KRB perfused the carotid body for 2 min. The stopcock was returned to its original position, allowing blocker-free hypoxic blood to perfuse the carotid body once again. With this protocol we found 1) the cholinergic blockers reduced the carotid body response to hypoxic KRB in a dose-dependent manner; 2) carotid baroreceptor activity was not reduced by the blockers, suggesting that the action of the blockers was not nonspecific (whereas lidocaine rapidly reduced both chemoreceptor and baroreceptor activity); 3) inclusion of the blockers in perfused hypoxic blood also reduced neural output from the carotid body; and 4) the blockers reduced the carotid body's neural response to hypoxic KRB containing substance P (20 micrograms/100 ml), suggesting that substance P may be linked to ACh in the carotid body. We conclude that these data provide good evidence supportive of an excitatory role for ACh in carotid body hypoxic excitation.