Gerkens J F
Faculty of Medicine, University of Newcastle, N.S.W., Australia.
J Pharmacol Methods. 1988 Apr;19(2):135-47. doi: 10.1016/0160-5402(88)90034-4.
A comparison was made of the endothelium-dependent vasodilatation produced by acetylcholine (Ach) in rat-tail arteries perfused with Krebs solution or whole rat blood. Segments of the tail artery of the rat were cannulated at both ends mounted in an organ bath and perfused at a constant 3 ml/min. Blood perfused the tail artery via an extra corporeal circuit by being withdrawn from and returned to a conscious donor rat previously prepared with exteriorized indwelling carotid artery and jugular vein cannulae. Perfusion pressure was increased by constricting the tail artery with an infusion of noradrenaline into the perfusate. In arteries perfused with Krebs solution, the infusion for 1 min of Ach at 10(-6) M maximally reduced perfusion pressure. However, when arteries were perfused with blood, the infusion of Ach calculated to produce a concentration of 10(-5) M in the blood, produced very little response. A higher concentration, 10(-4) M, produced a maximal dilatation. Treatment of the donor rat with 0.02 mg/kg physostigmine IV potentiated the response to 10(-5) M Ach. In Krebs-perfused vessels, physostigmine 10(-6) M did not potentiate Ach responses. Methacholine, which is more resistant to cholinesterase, was more potent than Ach in blood-perfused tail arteries. Removal of the endothelium of the tail artery blocked responses to Ach in the blood-perfused vessels. It is concluded that Ach can produce an endothelium-dependent dilatation in a vessel perfused with whole blood, although Ach in blood is susceptible to inactivation by cholinesterase.
