Effects of gamma-aminobutyric acid agonists on the isolated perfused rat kidney

The effects of gamma-aminobutyric acid (GABA) agonists were studied in the isolated perfused rat kidney. Perfusions were performed at constant flow with modified Ringer-Krebs solution. The GABA(A) agonist muscimol (0.1-75 mu M) induced an increase in fractional excretion of water and sodium without promoting hemodynamic changes. These tubular changes were inhibited by atropine pretreatment. Thus, a possible modulation of tubular transport mechanisms via GABA(A) receptors acting on cholinergic system could be suggested. Muscimol was unable to modify the renal vascular resistance either at basal conditions or in noradrenaline-pretreated preparations. However, the GABA(A) antagonist bicuculline (50 mu M) evoked an increased perfusion pressure. Despite the speculation that endogenous GABA could result in a maximal activation of these GABAergic processes, nonspecific binding sites for bicuculline should be considered. The GABA(B) agonist baclofen (0.05-500 mu M) elicited a raised perfusion pressure and diminished glomerular filtration rate, accompanied by an increment in fractional excretion of water, sodium and glucose. These findings suggest a major GABA(B) receptor-mediated vasoconstriction at the afferent arteriole level. Proximal tubular structures seem to be a biological target for baclofen. GABA (0.05-1000 mu M) evoked changes similar to those described for baclofen, although the glomerular filtration rate was not. diminished. Data from this study indicate that the GABA system may be involved in the modulation of rat renal function.