The pressor response to acetylcholine in the atropinized dog resulted from an increase in cardiac output. The pressor response was attributed solely to the release of adrenaline from the adrenal medulla. After giving compound P-286 (N-diethylaminoethyl-N-isopentyl-N'N'-di-isopropylurea) to these dogs, acetylcholine lowered blood pressure, owing to a decrease in total peripheral resistance in the absence of an increase in cardiac output. P-286 presumably blocked the liberation of adrenaline from the adrenal glands by acetylcholine. The blood vessels contributing to the fall in peripheral resistance were not in the intestines. The fall in blood pressure was not blocked by dichloroisoprenaline and it was still present in dogs treated with reserpine. It is suggested that the fall in blood pressure was due to stimulation of ganglion cells subserving vasodilatation.The pressor action of an intravenous injection of acetylcholine into the atropinized dog is reversed after the release of catechol amines from the adrenal medulla has been blocked by N-diethylaminoethyl-N-isopentyl-N'N'-di-isopropylurea, P-286 (Gardier, Abreu, Richards & Herrlich, 1960). The mechanism suggested by Shaw, Keogh & MacCallum (1948) and Shaw & MacCallum (1949) to explain the reversal, by various drugs, of the pressor response to acetylcholine after atropine is that acetylcholine stimulates sympathetic ganglion cells subserving vasodilator functions, the effect of which is revealed in the absence of pressor activity. In our opinion insufficient evidence has been available to substantiate this hypothesis.The studies reported here are concerned with the mechanism of the vasodepressor response to acetylcholine after administration of P-286 into the atropinized dog; in addition evidence is given that the pressor response to acetylcholine results from specific stimulation of the adrenal medulla.
METHODSAdult mongrel dogs, of either sex, were maintained in stage III, plane 3 of general anaesthesia with sodium pentobarbitone (30 mg/kg, intravenously); small supplementary doses (2.5 to 5 mg/kg) were administered when necessary. The usual dose of atropine sulphate was 1 mg/kg,
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