Prolonged hypotension and ultrastructural changes in sympathetic neurones following guanacline treatment

Changes in systemic blood pressure, catecholamine levels, fluorescent histochemistry and ultrastructure of sympathetic nerves both during and after cessation of chronic treatment of rats with guanacline (5 mg/kg/day) were examined. Comparative studies were also carried out on guanethidine. The systemic blood pressure fell steadily for the first 9–14 weeks in both guanethidine and guanacline-treated animals. Following cessation of drug treatment, the blood pressure of guanethidine-treated animals rose rapidly to normal levels, in contrast to guanacline-treated animals in which the rise was slow. Sections of sympathetic ganglion cells from guanacline-treated rats exhibited strong yellow autofluorescence which was shown by electron microscopy to consist of a massive deposition of lipoprotein granules (comparable to ‘aging pigment’). These granules were still present 12 weeks following cessation of treatment. No comparable changes were observed in guanethidine-treated animals. It is suggested that the cellular effects of guanacline might be related to the postural hypotension which persists in humans some months after withdrawal of therapy.