A study of long-term effects of guanethidine on peripheral noradrenergic neurones of the rat.

In long-term experiments in rats the effects of guanethidine sulphate on peripheral adrenergic neurons in the heart, the vas deferens, the superior cervical ganglion and the ganglion innervating the vas deferens were studied in relation to the dosage and route of administration of the drug by biochemical, histofluorimetric and electron-microscopic methods. When administered daily in very high doses, i.e. 180 mg/kg orally or 25 mg/kg intraperitoneally, for several weeks guanethidine was found to induce toxic effects which appeared to be a result of mitochondrial changes in the ganglion cells. These changes were not directly related to the decrease in catecholamine content and the capacity of the neurones to retain exogeneous transmitter. The short neurones innervating the vas deferens appeared to be the structures most sensitive to guanethidine. As in the other tissues, however, the changes in these structures proved reversible to a considerable extent upon cessation of high-dose treatment. The structural changes induced in the animal by toxic doses of guanethidine are considered to have no bearing upon the pharmacological action of the drug under practical conditions.