An Assessment of the Effectiveness of Neonatal Treatment With Guanethidine as a Means of Producing Sympathectomy

Abstract

1 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.2 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.3 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.4 The blood pressure response to acute bilateral adrenalectomy was similar in control and guanethidine-treated rats. 5 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.6 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. 7 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. 8 Despite the impaired efferent sympathetic nerve activity in rats treated neonatally with guanethidine, compensatory mechanisms permit adequate cardiovascular control in the resting state.

The Influence of Neonatal Treatment with Guanethidine on the Development of Isolation-Induced Hypertension in Adult Rats

“…Although we accept that the systolic blood pressure recorded by the tail-cuff method may not always truly represent systemic arterial blood pressure in guanethidine-treated rats (see above), it is clear from the second part of our investigation that the failure to demonstrate isolation-induced hypertension in those animals was not due to the method of blood pressure measurement since, when blood pressures were measured directly, the control, isolated rats were hypertensive whereas the guanethidine-treated rats were not. Within each group of rats that had received guanethidine, there were some animals which did show slight increases in blood pressure after isolation; this finding bears out our previous observations [5] of a variation between different animals in the extent of damage to the noradrenergic nerves.…”

“…Furthermore, when systolic blood pressures were recordable they were found to be lower in group-housed guanethidine-treated rats than in control animals (see the Results section); this was not the case in our earlier experiments in which arterial blood pressures were measured directly [5]. For these reasons the experiment was repeated and, at the end of the period of isolation, arterial blood pressures were measured directly.…”

“…The rats used in the first part of this study were treated at the same time as those used in our previous study [5] and in some cases were littermates. In that study we found, on average, a 90% reduction in ventricular noradrenaline content and a 74% reduction in atrial noradrenaline content in adult rats which had received guanethidine neonatally [S]; we believe that it is reasonable to assume that the animals used presently were similarly affected.…”

Angiotensin II-mediated catecholamine release during the pressor response in rats

“…The release of AD from the adrenal glands during the presssor response to ANG II may contribute to blood pressure regulation due to enhanced adrenoceptor responsiveness. Some investigators have sug¬ gested that adrenal medullary hyperactivity sustains blood pressure in the absence of an intact sympathetic nervous system in conscious rats (Bennett et al 1982). How¬ ever, there is little evidence of a significant role for adrenal catecholamine release in the pressor response to physiological levels of ANG II in vivo.…”

“…It is generally accepted that guanethidine, a noradrenergic neurone blocking agent, destroys peripheral sympathetic nerves when administered chronically to newborn rats in high doses (Mills et al 1986), possibly via an immune-mediated mechanism (Manning et al 1983). There are few data in the literature regarding plasma catecholamine levels following guanethidine treatment; the catecholamine contents in sympathetically innervated tissues are usually used as a measure of chemical sympathectomy in rats (Johnson et al 1976, Bennett et al 1982, Julien et al 1989, Lo et al 1991.…”