Modification and characterization of the permanent sympathectomy produced by the administration of guanethidine to newborn rats.

The administration of guanethidine to newborn rats has been shown to produce a permanent sympathectomy with potential advantages over immunosympathectomy and 6-hydroxydopamine-induced chemical sympathectomy. In this paper, we report on a revised treatment regimen involving initiation of treatment (50 mg/kg/day) on day 7 after birth and continuing for 3 weeks. Animals treated by this protocol have a low mortality rate (approx. 10% above saline-treated controls) and no permanent growth deficit. Analysis of tyrosine hydroxylase activity in and light microscopic examination of superior cervical ganglia of the guanethidine-treated animals indicate complete destruction of sympathetic neurons by the end of the second week of treatment. During and after treatment there are no decreases in norepinephrine in whole brain of the treated animals. Norepinephrine levels in peripheral tissues are markedly reduced at both 9 and 16 weeks of age. Stimulation of vasomotor outflow produces no increase in blood pressure in guanethidine-treated rats at 9 or 26 weeks of age, indicating a complete and permanent functional denervation of the vasculature. The adrenal glands of the guanethidine-treated animals are not destroyed, but rather respond, apparently by transsynaptic induction, with increases in tyrosine hydroxylase and epinephrine content. Interestingly, despite the continued deprivation of a peripheral sympathetic nervous system in these animals. adrenal tyrosine hydroxylase and epinephrine levels return to control levels by 10 weeks of age. These data indicate that administration of guanethidine to newborn rats produces a very complete and permanent sympathectomy with significant advantages over immunosympathectomy and 6-hydroxydopamine-induced chemical sympathectomy.