Chronic guanethidine treatment of female rats including effects on the fetus

Adult virgin female rats were injected daily with low doses (5 or 10 mg/kg) or a high dose (30 mg/kg) of guanethidine for 12 or 18 weeks respectively. 'Short' and 'long' noradrenergic neurones were unaffected by low doeses. This contrasts markedly to earlier findings in male rats in which long-term damage of 'short' noradrenergic neurones occurred, and indicates a basic difference between 'short' noradrenergic neurones in male and female rats. Widespread degeneration of both types of neurones followed treatment with high doses and little reinnervation was observed 8 weeks after cessation of treatment. Fertility, pregnancy and litter size were apparently unaffected. Some teratogenic effects were observed in the offspring of female rats treated with guanethidine (10 or 25 mg/kg/day) before and throughout pregnancy. However, these effects had largely disappeared by the time the offspring were 10 weeks old. Since noradrenergic neurones of newborn rats are particularly sensitive to damage by guanethidine it would appear that either very little guanethidine crosses the placental barrier or that noradrenergic neurones are not susceptible during prenatal development to the cytotoxic effects of guanethidine.