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Intracerebroventricular (i.c.v.) administration of JA116a, induces an increase in urinary volume and sodium excretion in conscious male hydrated rats. The involvement of brain dopaminergic neurons in the JA116a renal action was investigated. Diuretic and natriuretic action of JA116a was blocked by haloperidol pretreatment. The renal effect was prevented by selective dopaminergic neuron, denervation by i.c.v. administration of 6-hydroxydopamine in combination with desmethylimipramine. Our results suggest that JA116a acts centrally, at least in part, via an interaction with endogenous dopamine neurons.

1. Intracerebroventricular (IVT) administration of rat atrial natriuretic factor (ANF) (99-126) to conscious male hydrated rats induces a dose-dependent increase in urine and sodium excretion. The possible involvement of brain dopaminergic system in the IVT-ANF-induced diuresis and natriuresis was evaluated. 2. Central sympathectomy (6-OHDA, 250 micrograms/5 microliters, IVT; 72 and 48 hr before IVT-ANF) inhibited both the diuretic and the natriuretic action of centrally administered ANF, suggesting that in the brain ANF requires the integrity of central noradrenergic and/or dopaminergic systems function for its actions. 3. Intracerebroventricular injection of haloperidol and intragastric administration of domperidone prevent the diuretic and natriuretic response to centrally administered ANF. 4. Our data suggest a neuromodulatory action of ANF within the brain and demonstrate an interaction of the peptide with brain dopaminergic systems.

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Intracerebroventricular (ICV) administration of rat atrial natriuretic peptide (99-126) (rANP) to conscious male hydrated rats resulted in a dose-related increase in urinary volume and sodium excretion over a 6-h period of urine collection. A diminished mineralocorticoid effect on the kidneys may explain the natriuretic phenomenon. This hypothesis was tested by ICV rANP injection (1.25 microgram/5 microL) in conscious hydrated rats pretreated beforehand with d-aldosterone (20 micrograms/kg, ip). Although the absolute amount of sodium excreted was reduced, aldosterone did not affect rANP-induced sodium output at 1 and 3 h. Rats that were sham-operated or bilaterally adrenalectomized after 4 days were pretreated with aldosterone and given an oral water load followed by ICV rANP or saline. The possible participation of the peripheral sympathetic nervous system in the central action of rANP was evaluated in rats pretreated with 6-hydroxydopamine. In sympathectomized and adrenalectomized rats natriuresis and diuresis were still evident after rANP. Our results indicate that the natriuretic effect of ICV rANP is independent of mineralocorticoids. Likewise, diuresis and natriuresis can occur in the absence of the adrenal glands and are independent from the neural tone that the adrenergic system exerts on sodium reabsorption.