Effect of Tetraethyl Pyrophosphate on Sympathetic Ganglionic Activity

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Abstract
The nicotinic effect of various doses of ACh was measured by the pressor response in atropinized dogs treated with tetraethyl pyrophosphate (TEP). Ten [gamma] of TEP/kg. elicited pressor responses with moderate doses of ACh (0.05-0.10 mg./kg.). With increasing doses of TEP, the pressor response to 0.125 and 0.25 mg./kg. of ACh could be measured, and a curve relating TEP concns. with the magnitude of the response could be drawn. Continued admn. of TEP decreased the pressor response of ACh until none could be elicited at TEP levels of 70 mg./kg. Atropinized dogs survived with as much as 140 mg./kg. TEP proved to be the most powerful antiesterase yet reported. The initial maximal pressor response to ACh appears at: DFP, 15-20 mg./kg.; eserine, 0.5mg./kg.; hexaethyltetraphosphate (HETP), 0.5 mg./kg.; and TEP, 0.1 mg./kg. The present study of TEP substantiates the assumption that the measurements of the pressor responses to standard doses of ACh in the presence of varying concns. of different anticholinesterases can be used as an in vivo estimate of the inactivation of the cholinesterase. The inhibition of the cholinesterase is obtained in vivo with smaller concns. of the antiesterases, so that this method is more sensitive than the in vitro method. The efficiency of TEP is remarkable since, in the presence of a wide range of its concns., as small a dose of ACh as 0.8 [gamma]/kg. is sufficient to elicit pressor responses. The 2d of 2 peaks of the pressor response of ACh, which occurs at considerable levels of TEP from 15 to 20 mg./kg., is of interest. A similar peak occurs when eserine is used. Also, the pressor effects of nicotine followed a double-peak curve with increasing amts. of eserine. It is suggested that the biphasic response to ACh elicited within a wide range of concns. of different antiesterases is due to the effect of the latter on the sympathetic ganglia. The ganglia are first depressed and then, with higher concns. of the antiesterases, rendered more responsive.