Role of Mineralocorticoids in the Natriuresis of Water Immersion in Man

The role of aldosterone suppression in mediating the natriuresis of water immersion was assessed in six normal male subjects. All subjects were studied on four occasions while they were in balance on a diet containing 150 mEq of sodium and 100 mEq of potassium daily: during a control period, following deoxycorticosterone acetate (DOCA) treatment for 24 hours (Cont + DOCA), during water immersion to the neck (immersion), and during water immersion following DOCA treatment (Imm + DOCA). Immersion resulted in highly significant increases in the rates of sodium and potassium excretion compared with control beginning in the first hour. Although treatment with DOCA decreased the natriuresis of immersion ( P < 0.01), the rate of sodium excretion was still three- to fourfold greater during Imm + DOCA than it was during the comparable Cont + DOCA periods ( P < 0.01). Cessation of water immersion resulted in a marked decrease in urine flow and free water clearance occurring within the initial 30 minutes of recovery ( P < 0.005). Although the rate of sodium excretion also decreased following cessation of immersion, it continued to exceed both preimmersion values ( P < 0.01) and the comparable control values throughout the recovery hour ( P < 0.01). These observations suggest that the natriuresis of immersion cannot be completely accounted for by immersion-induced suppression of aldosterone. The continuing natriuresis occurring despite the progressive volume contraction induced by immersion suggests that the natriuretic stimulus is sufficiently potent to override the compensatory mechanisms which are known to participate in defense of volume homeostasis. Furthermore, the delay in the disappearance of the natriuresis suggests that a humoral factor rather than more rapidly acting hemodynamic and neural mechanisms may mediate the natriuresis

Increased renal glomerular endothelin-1 release in gentamicin-induced nephrotoxicity

Gentamicin-induced acute renal failure is characterized by a decrease in renal plasma flow and creatinine clearance. Endothelins (ET) are potent renal vasoconstrictors. The aim of this work is to assess the role of ET-1 in gentamicin-induced renal failure. Renal glomerular release of ET-1 was measured in rats with gentamicin-induced nephrotoxicity (100 mg/kg/day, s.c. for 2, 4 or 6 days). Glomeruli were isolated and incubated for 24 h in RPMI-1640. Glomerular supernatant and plasma concentration of ET-1 were measured by RIA. Renal failure was assessed by insulin, para-aminohippuric and creatinine clearance and histological studies. Gentamicin induced a dose number-dependent increase in plasma creatinine and a decrease in creatinine clearance. This was accompanied by a marked decrease in inulin and para-aminohippuric acid clearance, as well as by a marked tubular necrosis, without alterations in glomerular structures. Plasma ET-1 concentration and glomerular ET-1 release were also increased in gentamicin-treated rats. When 10−5 m gentamicin was added to control glomeruli, ET-1 production was not modified (36.4 ± 2.2 vs. 35.2 ± 1.7 pg/ml/24 h). All these results suggest that elevated ET-1 plasma levels and increased glomerular release of ET-1 could mediate, at least in part, the decrease in glomerular filtration rate observed in gentamicin-induced ARF