Serotonin and norepinephrine-dependent effects of fenfluramine on plasma renin activity in conscious male rats.

Administration of DL-fenfluramine to male rats caused an initial rise, followed by a sustained decrease in plasma renin activity. Both the increase, which reached a maximum at 30 min and the decrease, which was maximal at 4 hr after administration of fenfluramine, were dose-dependent. Pretreatment with either of the blockers of serotonin uptake, fluoxetine or indalpine blocked the increase in plasma renin activity induced by fenfluramine at 30 min, but did not affect the decrease at 4 hr after injection. Similarly, pretreatment with the inhibitor of the synthesis of serotonin, p-chlorophenylalanine methylester (PCPA) blocked the initial (30 min) but not the delayed (4 hr) effect of fenfluramine on plasma renin activity. The initial stimulation of secretion of renin by a submaximal dose (2 mg/kg, i.p.) of fenfluramine was potentiated by pretreatment with the precursor of serotonin L-tryptophan (100 mg/kg, i.p.). Pretreatment with the blocker of the uptake of norepinephrine, desipramine did not prevent the initial (30 min) effect but completely prevented the delayed (4 hr) effect of fenfluramine on plasma renin activity. These results suggest that the initial effect of fenfluramine is mediated via a serotonergic mechanism while the delayed, but long-lasting suppression of plasma renin activity, is mediated via a noradrenergic mechanism.