Acute ureteral obstruction and glomerulotubular function in rats.

Urinary tract obstruction is a common cause of acute renal failure (ARF). During unilateral ureteral obstruction (UUO) arteriolar vasoconstriction, increase in tubular pressure, and ultrafiltrate retrodiffusion occur. We studied renal function of rats with surgical UUO for 24 hr. After this period of UUO, the contralateral kidney was removed and the right ureter was deobstructed. The control uninephrectomized group consisted of normal rats submitted to left uninephrectomy (UNx). Functional studies were performed 12 and 24 hr, and 7 days after deobstruction and UNx. We measured creatinine clearance, and fractional excretion of sodium and lithium. Using conventional formulas we calculated fractional proximal and distal sodium reabsorption. Initially we observed a reduction in glomerular filtration rate (GFR) after deobstruction (12 and 24 hr). However, after 7 days, the GFR was significantly higher in deobstructed rats than in controls (340.3 +/- 18.3 vs. 286.4 +/- 9.3 microL/min/100 g, p < 0.01). The dry kidney weight was also increased in these rats. The fractional sodium excretion was increased in deobstructed rats, mainly in early studies (12 and 24 hr). Whereas fractional proximal reabsorption was reduced in both groups, the fractional distal reabsorption was significantly decreased in the deobstructed group compared to UNX controls (93.9 +/- 0.9 vs. 98.9 +/- 0.1% after 24 hr, p < 0.01). Our data showed that UUO influenced both glomerular and tubular functions. A salient finding was the overcorrection of GFR 7 days after deobstruction. The renal release of hormones and growth factors could mediate these alterations in renal function through their vascular, tubular, and proliferative actions.

Effects of nifedipine and platelet activating factor antagonist (BN 52021) in glycerol-induced acute renal failure in rats.

We studied the actions of nifedipine and the platelet activating factor (PAF) antagonist BN 52021 on renal and tubular function in glycerol-induced acute renal failure (Gly-ARF). The tubular handling of sodium was evaluated through the lithium clearance method in awake rats in metabolic cages. The sequential analysis of tubular function 3, 6, 12, and 24 h after Gly-ARF showed a sharp decrease in fractional proximal Na reabsorption (FPRNa)--control 74.1 +/- 12.5%, 3 h: 79.5 +/- 6.0%; 6 h: 41.8 +/- 15.9%; 12 h: 22.9 +/- 17.9%; and 24 h: 31.1 +/- 16.2% (p < 0.001) while fractional distal Na reabsorption (FDRNa) did not change during the study. The effect of nifedipine (20 mg/kg p.o.) and BN 52021 (1 mg/kg i.p.) were evaluated 24 h after the induction of Gly-ARF. Both drugs attenuated the reduction in creatinine clearance (control 431.8 +/- 108.2, glycerol 96.7 +/- 43.8, glycerol plus nifedipine 264.9 +/- 103.5, and glycerol plus BN 52021 188.9 +/- 69.8 microL/min/100 g, p < 0.001). However, only nifedipine could keep FPRNa higher than untreated rats (58.3 +/- 13.2 vs. 31.1 +/- 16.2%, p < 0.05) and reduced the tubular necrosis on histologic semiquantitative analysis. Our data showed that nifedipine and BN 52021 could protect against filtration failure in Gly-ARF but that only nifedipine reduced the proximal tubular lesion.

Renal sodium handling after noradrenergic stimulation of the lateral hypothalamic area in rats.

1. The participation of special nephron segments in the renal control of sodium handling after adrenergic stimulation was investigated by determining lithium clearance in groups of 5-12 male Wistar rats (230-300 g) microinjected with noradrenaline into the lateral hypothalamic area (LHA). 2. Microinjection of noradrenaline (12.5 to 100.0 nmol/microliters) into the LHA promoted a significant decrease in proximal sodium reabsorption (controls, 86.5 +/- 1.3; 12.5, 81.4 +/- 2.0; 25.0, 72.6 +/- 2.4; 50.0, 75.4 +/- 1.8 and 100.0, 77.2 +/- 1.7%) and a dose-related increase in distal sodium reabsorption (control, 13.4 +/- 1.6; 12.5, 18.4 +/- 1,25.0, 26.9 +/- 2.9; 50.0, 24.1 +/- 2.7; 100.0, 22.1 +/- 1.9%) with no significant changes in creatinine clearance. Fractional sodium reabsorption after different noradrenaline concentrations was significantly reduced in the proximal nephron sites up to the concentration of 25.0 nmol/microliter. Beyond this concentration, a smaller but progressive increase in fractional sodium reabsorption was observed in the post-proximal segment. 3. These findings suggest an effective participation of proximal and post-proximal nephrons in natriuresis after lateral hypothalamic noradrenergic stimulation.

Renal sodium handling after noradrenergic stimulation of the lateral hypothalamic area in rats

The participation of specific of special nephron segments in the renal control of sodium handling after adrenergic stimulation was investigated by determining lithium clearance in groups of 5-12 male Wistar rats (230-300 g) microinjected with noradrenaline into the lateral hypothalamic area (LHA). Microinjection of noradrenaline (12.5 to 100.0 nmol/ul) into the LHA promoted a significant decrease in proximal sodium reabsorption (control, 86.5 ñ 1.3; 12.5,81.4 ñ 2.4; 50.0, 75.4 ñ 1.8 and 100.0,77.2 ñ 1.7%) and a dose-related increase in distal sodium reabsorption (control, 13.4 ñ 1.6; 12.5, 18.4 ñ 1.25.0,26.9 ñ 2.9; 50.0,24.1 ñ 2.7; 100.0,22.1 ñ 1.9%) with no significannt changes inm creatinine clearance. Fractional sodium reabsorption after different noradrenaline concentrations was significantly reduced in the proximal nephron sites up to the concentration of 25.0 nmol/ul. Beyond this concentration, a smaller but progressive increase in fraqctional sodium reabsorption was observed in the post-proximal segment. These findings suggest an effective participation of proximal and post-proximal nephrons in natriuresis after lateral hypothalamic noradrenergic stimulation

Renal water handling evaluated by lithium clearance following adrenergic and cholinergic stimulation of the lateral hypothalamic area.

Male Wistar rats weighing 230-300 g were used to characterize the participation of adrenergic and cholinergic receptors of the lateral hypothalamic area (LHA) in the control of renal water excretion. Since stimulation of adrenergic or cholinergic receptors has no effect on glomerular filtration rate, the antidiuresis and significant delay in urinary flow observed after lateral hypothalamic stimulation with carbachol (CCh) (0.036 +/- 0.005 to 0.019 +/- 0.003 microliters min-1 100 g body weight-1) and noradrenaline (Nad) (0.024 +/- 0.005 to 0.025 +/- 0.004 microliters min-1 100 g body weight-1) are secondary to an increase in distal tubular fluid reabsorption (DFR). Data are reported as means +/- SEM for ten rats in each group. Tubular water handling measured by lithium clearance demonstrated that LHA simulation with CCh (2.8 nmol in 1 microliter) and Nad (30.0 nmol in 1 microliter) leads to a significant reduction in proximal water reabsorption (CCh, 93.3 +/- 2.6 to 85.4 +/- 1.4%; Nad, 92.7 +/- 0.9 to 88.6 +/- 1.3%), with a simultaneous and significant increase in fluid reabsorption along the post-proximal nephron segments when compared to control (CNa) (CCh, 6.7 +/- 0.7 to 14.5 +/- 1.1%; Nad, 8.2 +/- 0.8 to 11.4 +/- 1.6%). These effects are blocked by muscarinic (atropine, 5 nmol in 1 microliter) and alpha-1 adrenoceptors (prazosin, 4 nmol in 1 microliter) antagonists. The results indicate the effective participation of the post-proximal nephron in the antidiuresis occurring after cholinergic and adrenergic LHA stimulation.

Renal water handling evaluated by lithium clearance following adrenergic and cholinergic stimulation of the lateral hypothalamic area

Male Wistar rats weighing 230-3--g were used to characterize the participation of adrenerg and cholinergic receptors of the lateral hypothalamic area (LHA) in the control of renal water excretion. Since stimulation of adrenergic or cholinergic receptors has no effect on glomerular filtration rate, the antidiuresis and significant delay in urinary flow observed after lateral hypothalamic stimulation with carbachol (CCh) (0.036 ñ 0.005 to o.019 ñ 0.003 µlmin-1 100g body weight-1) and noradrenaline (Nad) (0.024 ñ 0.005 to 0.025 ñ 0.004 µl min-1 100g body weight-1) are secondary to an increase in distal tubular fluid reabsorption (DFR). Data are reported as means ñ SEM for ten rats each group. Tubular water measured by lithim clearance demonstrated that LHA stimulation with CCh (2.8 nmol in 1 µl) and Nad (30.0 nmol in µl) leads to a significant reduction in proximal water reabsorption with CCh, 93.3 ñ 2.6 to 85.4 ñ 1.4%; Nad, 92.7 ñ0.9 to 88.6 ñ 1.3%), with a simultaneous and significant incrase in fluid reabsorption along the post-proximal nephrom segments when compared to control (CNa) (CCh, 6.7 ñ 0.7 to 14.5 ñ 1.1%; Nad 8.2 ñ 0.8 to 11.4 ñ 1.6%) These effects are blocked by muscarinic (atropine, 5 nmol in 1 µl) and alpha-1 adrenoceptors (prazosin, 4 nmol in 1 µl) antagonists. The results indicate the effective participation of the post-proximal nephron in the antidiuresis occurring after cholinergic and adrenergic LHA stimulation