Natriuresis induced by intracerebroventricular diazepam in rabbits

ABSTRACT

The renal function is under regulatory influence of central nervous system (CNS), in which various neurotransmitter and neuromodulator systems take part. However, a possible role of central GABA-benzodiazepine system on the central regulation of renal function has not been explored. This study was undertaken to delineate the renal effects of diazepam. Diazepam, a benzodiazepine agonist, administered into a lateral ventricle (icv) of the rabbit brain in doses ranging from 10 to 100 microgram/kg, elicited dose-related diuresis and natriuresis along with improved renal hemodynamics. However, when given intravenously, 100 mug/kg diazepam did not produce any significant changes in all parameters of renal function and systemic blood pressure. Diazepam, 100 mug/kg icv, transiently decreased the renal nerve activity (RNA), which recovered after 3 min. The plasma level of atrial natriuretic peptide (ANP) increased 7-fold, the peak coinciding with the natriuresis and diuresis. Muscimol, a GABAergic agonist, 1.0 mug/kg given icv, elicited marked antidiuresis and antinatriuresis, accompanied by decreases in systemic blood pressure and renal hemodynamics. When icv 0.3 microgram/kg muscimol was given 3 min prior to 30 mug/kg of diazepam icv, urinary flow and Na excretion rates did not change significantly, while systemic hypotension was produced. These results indicate that icv diazepam may bring about natriuresis and diuresis by influencing the central regulation of renal function, and that the renal effects are related to the increased plasma ANP levels, not to the decreased renal nerve activity, and suggest that the effects may not be mediated by the activation of central GABAergic system.