Unique resistance to guanethidine-induced chemical sympathectomy of spontaneously hypertensive rats: a resistance overcome by treatment with antibody to nerve growth factor.

Abstract

The chronic administration of high doses of guanethidine to rats produces complete destruction of the peripheral sympathetic nervous system. In a study of the effect of guanethidine-induced sympathectomy on the development of hypertension is spontaneous hypertensive rats (SHR, Okomoto strain), only a partial sympathectomy could be produced as assessed by biochemical parameters (tyrosine hydroxylase activity in ganglia and tissue norepinephrine concentrations) and by evaluation of response to stimulation of vasomotor outflow in pithed rat preparations. Other strains of rats (Sprague-Dawley, American Wistar, Kyoto Wistar) were uniformly sensitive to guanethidine sympathectomy. The resistance to guanethidine was not due to a lower accumulation of guanethidine in the neurons of SHR. Addition to the guanethidine treatment of low doses of antibody to nerve growth factor (NGF), which itself produced only a modest sympathectomy, resulted in an almost complete sympathectomy. SHR did not become hypertensive when sympathectomized by combined guanethidine-anti NGF. These results show that the sympathetic neurons of SHR differ from those of other strains with respect to sensitivity to guanethidine cytotoxicity and suggest the possibility of a role for NGF in that altered responsiveness.