Central serotonergic influences on renal electrolyte and water excretion

These studies examined the effects of altered activity or levels of serotonin (5-HT) in the central nervous system (CNS) on renal water and excretion of electrolytes and on arterial blood pressure. Rats were implanted with intracerebroventricular cannulae and then continuously hydrated with a hypotonic solution in order to induce a diuresis. In two separate experimental series, samples of urine were collected before and after intraventricular (i.v.t.) administrations of drug, and the effects on the excretion of sodium were determined. In the first experimental series, 5-HT in the CNS was manipulated by intraventricular administration of p-chloroamphetamine (PCA), an agent known to increase synaptic concentrations of 5-HT. Significant increases in urinary excretion of sodium (UNa V) and the Na/K ratio were observed after the administration of p-chloroamphetamine (200-600 micrograms i.v.t.). p-Chloroamphetamine in large doses also increased blood pressure and antidiuresis. The natriuresis, but not the pressor or antidiuretic responses, were attenuated by pretreatment with either p-chlorophenylalanine, an inhibitor of tryptophan hydroxylase, or fluoxetine, a drug which inhibits the release of 5-HT following the administration of p-chloroamphetamine. Thus, the natriuretic response appeared to be due to a p-chloroamphetamine produced increase of synaptic 5-HT. A further test of the role of 5-HT in the central control of sodium excretion was made in a second experimental series where hydrated rats received intraventricular injections of 5-HT. After direct application of 5-HT to the CNS, significant increases in UNa V and in the Na/K ratio were observed, concomitant with depressor effects.(ABSTRACT TRUNCATED AT 250 WORDS)