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  • Title: Guanethidine induced sympathectomy in the adult rat. II. Functional effects following chronic administration.
    Author: Nielsen GD.
    Journal: Acta Pharmacol Toxicol (Copenh); 1977 Sep; 41(3):209-17. PubMed ID: 578649.
    Abstract:
    Guanethidine sulphate in doses of 5 and 40 mg/kg was administered intraperitoneally to adult rats daily for three months followed by discontinuation of administration for one day or three months. Following guanethidine 40 mg/kg a loss of approximately 95% of the nerve cells of the superior cervical ganglion was observed. No changes were observed after 5 mg/kg. The average mean arterial blood pressure (measured under chloralose-urethane anaesthesia) was lowered by 33 and 54 mmHg by guanethidine 40 mg/kg for three months followed by discontinuation for one day and three months respectively. The heart rate was unchanged. Guanethidine 5 mg/kg did not change any of these parameters. The increase in blood pressure and heart rate caused by intravenously administered noradrenaline was greatly enhanced following guanethidine 40 mg/kg, whereas only small changes were observed following 5 mg/kg. Following discontinuation for one day of 40 mg/kg for three months the potency ratios for the mean arterial blood pressure and the mean heart rate were 31 and 21 respectively, after discontinuation for three months 44 and 17 respectively. The potency ratios following guanethidine 5 mg/kg were 1.5 to 2.0. No changes were observed in the weight of the suprarenal glands following guanethidine. The present investigation has demonstrated an almost total chemical sympathectomy by guanethidine 40 mg/kg for three months and a persistent hypersensitivity to noradrenaline even after discontinuation of medication for three months.
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