In most species, the effect of systemic intoxication with an anti-cholinesterase-for example, HETP (hexaethyltetraphosphate), TEPP (tetraethyl pyrophosphate), dyflos (diisopropylphosphorofluoridate), Tabun (ethyl NN-dimethylphosphoramidocyanidate), or neostigmine-is predominantly the production of a profound fall in blood pressure (Modell, Krop, Hitchcock and Riker, 1946;Heymans and Jacob, 1947;Lundholm, 1949;Burgen, Keele and Slome, 1949;Verbeke and Votava, 1949;Salerno and Coon, 1949;Holmstedt, 1951). We have recently noticed that the intravenous administration of the anti-cholinesterase " Sarin " (isopropyl methylphosphonofluoridate) to intact rats produces a sharp rise in blood pressure, then one or two oscillations about the point of increased pressure, followed by a very gradual fall in pressure over the next several minutes (10-180 min. in different animals) back to the pre-injection level (Fig. 1). The cause of this sustained rise in blood pressure produced by sarin has been investigated.
METHODSWhite rats of homogeneous strain and weighing 350-500 g. were used. They were anaesthetized with urethane (1.25 g./kg. subcutaneously), and polythene cannulae were inserted into the carotid artery, to record blood pressure, and into the femoral vein. (Fig. 2). With higher single doses (e.g. 90 Itg./kg.) the animal dies before the sustained rise in blood pressure has become established.Bilateral vagotomy does not affect the results, but if sarin is given to a spinal rat only a relatively slow, small and short-lasting increase in blood pressure is caused (Fig. 3). The failure of sarin to produce a sustained elevation of blood pressure in this experiment is not due to the low blood pressure presented by a spinal rat.
The capacity to potentiate the sedative action of pentobarbitone by the volatile oil of Indian Acorus calamus has been used to screen various fractions of the oil for the presence of the principle responsible. The methods used for the removal of the oxygenated components of the oil did not remove the active material. The results show that the active principle resides in the hydrocarbon fraction of the oil or in an oxygenated component not removed by the methods employed. The volatile oil from the European Acorus calamus showed activity similar to the oil from the Indian drug.
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