Anticholinesterases and the cholinergic link hypothesis with reference to the rabbit ear artery

1. Constrictor responses of the isolated perfused rabbit ear artery to electrical stimulation and to intraluminally applied noradrenaline and histamine have been studied before and after addition to the perfusate of the anticholinesterases neostigmine and physostigmine. 2. Both neostigmine (6×10(-5)-2.4×10(-4) mol/l) and physostigmine (6×10(-5)mol/l) caused a small but significant (P<0.05) increase in responses to electrical stimulation and to intraluminal noradrenaline and histamine. The degree of potentiation was similar for all three modes of stimulation, suggesting that neostigmine and physostigmine act at smooth muscle level rather than at nerve terminal level. 3. In the presence of a high potassium perfusate, the artery failed to respond to electrical stimulation but still responded to noradrenaline and histamine. In this medium, the potentiating action of neostigmine disappeared, suggesting that this action depends on the initial presence of a normal resting membrane potential in the arterial smooth muscle cells. 4. These results do not support the cholinergic link hypothesis, that acetylcholine is involved in the release of noradrenaline at adrenergic nerve terminals.