Effect of long-term treatment with guanacline or guanethidine on sympathetic function

Abstract

Rats were treated with guanacline or guanethidine, 5 mg/kg/day i.p. for 19 weeks. Blood pressure, noradrenaline levels and responses to stimulation of the spinal sympathetic outflow, isolated perfused mesenteric artery and tail artery were examined during and after cessation of treatment. Both drug treatments reduced blood pressure to the same extent. Afte cessation of the two treatments there was little difference between them in the recovery of blood pressure. In acute experiments, guanethidine was more potent than guanacline in reducing the pressor response to spinal stimulation. Chronic treatment with guanethidine reduced responses to spinal stimulation by 55% after 4 weeks and 69% after 19 weeks. Guanacline treatment produced no reduction after 4 weeks and only 37% reduction after 19 weeks. After cessation of treatment the responses of guanethidine-treated rats increased rapidly whereas in guanacline-treated rats the recovery of responses was slow. Both drug treatments reduced the mesenteric artery vasoconstrictor response after 4 and 19 weeks. After cessation of treatment the responses recovered within 3 weeks. Guanethidine, but not guanacline, treatment reduced the tail artery vasoconstrictor response. Both treatments depleted heart noradrenaline by 65%. After cessation, repletion was similar for both drugs. It is suggested that the slow recovery of spinal stimulation responses after cessation of guanacline treatment reflects as persistent impairment of sympathetic function. This may be due to the ultrastructural changes known to be produced by long-term guanacline treatment.