Guanethidine Induced Sympathectomy in the Adult Rat. I. Functional Effects Following Subacute Administration

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Abstract
Guanethidine sulfate, an antihypertensive, 5 and 40 mg/kg was administered i.p. to adult rats for 4, 8, 14 and 28 days followed by discontinuation for 1 day, after administration for 28 days and additionally for 8, 14, 29 and 60 days. Under chloralose-urethane anesthesia the mean arterial blood pressure and the mean heart rate were determined and the response of these parameters to i.v. noradrenaline [norepinephrine, NA] 3-1600 ng was recorded. The blood pressure was not significantly changed after guanethidine 5 mg/kg but lowered by 40 mg/kg, the decrease being reversible on discontinuation. The response of both parameters to NA was increased by guanethidine depending on the dose. The hypersensitivity was partly reversible on discontinuation but a significantly increased sensitivity of the heart rate to NA was observed 60 days after discontinuation of guanethidine 40 mg/kg for 28 days. Histologically a profound loss of nerve cells of the superior cervical ganglion was observed following guanethidine 40 mg/kg, whereas no change was observed after 5 mg/kg. Guanethidine 5 mg/kg did not induce histological or permanent hemodynamic changes, whereas 40 mg/kg for 28 days resulted in an incomplete sympathectomy accompanied by a partially irreversible hypersensitivity to NA. There was no simple relation between the loss of ganglion cells and the hemodynamic changes and hence the hypersensitivity to NA was only in part due to the postganglionic sympathetic neuron destruction obtained by long term administration of large guanethidine doses.