An assessment of the effectiveness of neonatal treatment with guanethidine as a means of producing sympathectomy.

Abstract

Male Wistar rats were treated neonatally with guanethidine (following a protocol reported to produce a permanent peripheral sympathectomy) and the extent of the sympathectomy was assessed when the rats were mature. The noradrenaline content of right and left atria and the ventricles was markedly reduced in 9‐ and 26‐week old rats which had been treated with guanethidine. The extent of depletion in the ventricles was similar at both times but the atrial content increased between 9 and 26 weeks. Arterial blood pressures were not significantly different in 24–26‐week old conscious rats which had been treated neonatally with guanethidine compared to controls, but the baroreflex sensitivity, assessed by the lengthening of pulse interval in response to a pressor stimulus, was significantly less in the guanethidine‐treated rats. The blood pressure response to acute bilateral adrenalectomy was similar in control and guanethidine‐treated rats. Left atria and hepatic portal veins taken from 20–26‐week old rats which had been treated with guanethidine showed classical signs of a denervation supersensitivity, but the chronotropic responses of right atria to noradrenergic nerve stimulation and to noradrenaline were normal. Fluorescence histochemical studies on the right atria, irides and hepatic portal veins showed that the neonatal treatment had caused a variable degree of destruction both between and within animals. The findings are consistent with neonatal guanethidine treatment causing extensive damage to peripheral noradrenergic nerves. However, the sympathectomy is neither complete nor permanent. In the heart, there appears to be a selective re‐innervation of the atria. Despite the impaired efferent sympathetic nerve activity in rats treated neonatally with guanethidine, compensatory mechanisms permit adequate cardiovascular control in the resting state.