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 GABAA agonist muscimol (0.1-75 microM) 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 GABAA 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 GABAA antagonist bicuculline (50 microM) 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 GABAB agonist baclofen (0.05-500 microM) 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 GABAB receptor-mediated vasoconstriction at the afferent arteriole level. Proximal tubular structures seem to be a biological target for baclofen. GABA (0.05-1000 microM) 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.

Vascular and tubular actions of diazepam in isolated and perfused rat kidney.

The effects of diazepam were studied in the isolated rat kidney under conditions of constant flow. Kidneys were perfused with modified Ringer-Krebs solution. Diazepam produced a raised fractional excretion of water and sodium without hemodynamic changes, suggesting a direct effect on tubular transport mechanisms. Diazepam decreased renal perfusion pressure in a concentration-dependent fashion when kidneys were pretreated with either noradrenaline or potassium chloride. Similar responses were observed when 7-chloro-5-[4-chloro-phenyl]-1, 3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (Ro 5-4864) or clonazepam was used. These data provide evidence for a relaxant effect of benzodiazepines on preconstricted renal vasculature.

Estimation of bone turnover in climacteric women by the whole body retention of fluoride.

This paper reports the measurement of whole body retention using fluoride (WBRF) as an estimator of skeletal turnover in a group of climacteric women that received an oral dose of 700 mumol of sodium fluoride. WBRF is defined as 100(1-(urinary fluoride/fluoride load)). WBRF was significantly correlated with whole body retention of 99m-Tc-methylene-diphosphonate, the serum levels of the bone alkaline phosphatase and the urinary excretion of hydroxyproline. WBRF values ranged from 20% to 95% and were affected by calcium intake and the urinary calcium excretion. In normal subjects with high turnover, the measurement of serum alkaline phosphatase activity and/or urinary hydroxyproline excretion helps to distinguish these cases from patients with metabolic bone diseases due to metastases, Paget disease, etc. The fact that the fraction of fluoride not incorporated into bone is not further metabolized plus the accuracy, preciseness and rapidity of fluoride measurements in urine are the main advantages of this technique.