Brain catecholamines mediate the delayed reduction in renin release after injection of fenfluramine

The present studies examined whether brain or peripheral catecholaminergic mechanisms mediate the fenfluramine-induced reduction in plasma renin activity and concentration. Fenfluramine reduced plasma renin activity and concentration to 35% of basal levels in vehicle pretreated rats. This reduction was prevented in rats whose central catecholaminergic neurons were destroyed by i.c.v. injection of 6-hydroxydopamine (6-OHDA) two weeks prior to the experiment. In contrast, the suppressive effects of fenfluramine on plasma renin activity and concentration was not altered in rats that were surgically adrenal medullectomized and chemically sympathectomized by 6-OHDA. To determine whether alpha 2 adrenoceptors mediate the suppressive effects of fenfluramine, rats were pretreated with increasing doses of the alpha 2 adrenoceptor antagonist yohimbine 1 h before the administration of fenfluramine. Although yohimbine alone increased plasma renin activity and concentration, it did not prevent the suppressive effects of fenfluramine. In conclusion, the data suggest that central, but not peripheral catecholamines mediate the suppressive effect of fenfluramine on renin secretion. This effect is not mediated by alpha 2 adrenoceptors.