The present study investigated the early presence of inflammatory response in renal tissue of young offspring from diabetic mothers. The effect of L-arginine (L-arg) supplementation was also investigated. The offspring was divided into four groups: group CO (controls); group DO (diabetic offspring); group CA (CO receiving 2% L-arg solution) and group DA (DO receiving the 2% L-arg solution). Glycemia, arterial pressure and renal function were evaluated; gene and protein expression of pro-inflammatory cytokines were also measured. Blood pressure levels were significantly increased in 2 and 6 month-old DO rats, whereas L-arg administration caused a significant decrease in the DA group, at both ages. DO rats showed a significantly blunted glycemic response to exogenous insulin. In 2 month-old DO animals, renal protein expression of pro-inflammatory molecules was significantly increased. At six months of age, we also observed an increase in gene expression of pro-inflammatory molecules, whereas L-arg supplementation prevented this increase at both ages. Our data suggest that activation of inflammatory pathways is present early in the kidney of DO rats, and that L-arg can attenuate the expression of these markers of tissue inflammation. Our results also reinforce the concept that intrauterine environmental factors are a fundamental determinant in the development of metabolic and vascular diseases later in life.

The objective of the present study was to determine if treatment of diabetic rats with D-alpha-tocopherol could prevent the changes in glomerular and tubular function commonly observed in this disease. Sixty male Wistar rats divided into four groups were studied: control (C), control treated with D-alpha-tocopherol (C + T), diabetic (D), and diabetic treated with D-alpha-tocopherol (D + T). Treatment with D-alpha-tocopherol (40 mg/kg every other day, ip) was started three days after diabetes induction with streptozotocin (60 mg/kg, ip). Renal function studies and microperfusion measurements were performed 30 days after diabetes induction and the kidneys were removed for morphometric analyses. Data are reported as means +/- SEM. Glomerular filtration rate increased in D rats but decreased in D + T rats (C: 6.43 +/- 0.21; D: 7.74 +/- 0.45; D + T: 3.86 +/- 0.18 ml min-1 kg-1). Alterations of tubular acidification observed in bicarbonate absorption flux (JHCO3) and in acidification half-time (t/2) in group D were reversed in group D + T (JHCO3, C: 2.30 +/- 0.10; D: 3.28 +/- 0.22; D + T: 1.87 +/- 0.08 nmol cm-2 s-1; t/2, C: 4.75 +/- 0.20; D: 3.52 +/- 0.15; D + T: 5.92 +/- 0.19 s). Glomerular area was significantly increased in D, while D + T rats exhibited values similar to C, suggesting that the vitamin prevented the hypertrophic effect of hyperglycemia (C: 8334.21 +/- 112.05; D: 10,217.55 +/- 100.66; D + T: 8478.21 +/- 119.81 microm(2)). These results suggest that D-alpha-tocopherol is able to protect rats, at least in part, from the harmful effects of diabetes on renal function.

1. The influence of thyroparathyroidectomy on renal function and specifically on acid excretion was studied in rats with or without oral supplementation of calcium. 2. Thyroparathyroidectomy caused a significant decrease in glomerular filtration rate, in the urinary/plasma inulin ratio and in overall acid excretion. These changes were not corrected by calcium supplementation. 3. Rates of proximal tubular acidification were studied by means of double-barrelled resin/reference microelectrodes. Acidification half-time was significantly increased in both thyroparathyroidectomized and calcium-supplemented thyroparathyroidectomized rats (8.38 s and 7.40 s, respectively) compared with control rats (5.44 s). 4. When 10(-6) mol/l A23187, a calcium ionophore, was added to the luminal bicarbonate solution, the acidification half-time returned to 3.97 s in the thyroparathyroidectomized rats, whereas no significant changes were detected in the properties of acidification in the control rats. 5. These data show that parathyroid hormone and cellular calcium are important factors involved in proximal tubular H+ secretion, which appears to be largely dependent on a well-defined concentration range of these agents.

The effect of gentamicin, an aminoglycoside antibiotic, on renal function and especially on acid excretion was studied in normal and acidotic rats. The doses used were 1 (G₄) and 10 (G₄₀) times the suggested human therapeutic dose on a weight basis. After 10 days of each treatment, the glomerular filtration rate (GFR) was unchanged in G4 but fell significantly (p < 0.05) in G₄₀. In the acidotic groups (AG₄ and AG₄₀) there was an accentuated reduction in GFR, renal plasma flow and urine/plasma inulin ratio. Normal rats showed a normal acid excretion even with the high-dose treatment but, in the acidotic group, there was a significant decrease in ammonia excretion. The amount of bicarbonate excretion was significantly elevated in those groups, leading to a greater urinary pH. These results indicate that acute metabolic acidosis enhanced the nephrotoxic effects of gentamicin and impaired the excretion of an acid overload.

Parathyroid hormone (PTH) has multiple effects on water and electrolyte transport along the nephron. However, the influences of PTH and calcium on the urinary concentration ability are not fully understood. In this study, clearance and microperfusion studies were performed in thyroparathyroidectomized (TPTX) rats either supplemented (TPTX+Ca²⁺) or not with calcium added to the ingested food as CaCl₂ (1.6 g/100 g). Acid-base data and renal functional parameters were measured in TPTX and TPTX+Ca²⁺ rats. Additional studies were performed in the isolated inner medullary collecting tubules of intact and TPTX rats to evaluate the osmotic permeability of this segment in the presence of 10^–6M PTH added to the bath. In these experiments the possible influence of PTH on antidiuretic hormone induced changes of the osmotic permeability in TPTX and TPTX+Ca²⁺ rats was also investigated. In the TPTX+Ca⁺ group, the glomerular filtration rate increased significantly when compared to the TPTX group (6.04 ± 0.42 vs. 4.88 ± 0.20 ml·min^–1·kg^–1; p < 0.05), but the U/P inulin ratio remained lower than control values (30.8 ± 1.48 vs. 54.0 ± 3.5; p < 0.05), which suggests that normal levels of PTH are necessary to maintain the concentrating ability. In a group of TPTX rats, an acute infusion of PTH (0.5 µg·min^–1·kg^–1) significantly decreased the urinary flow and increased the renal plasma flow, results that agree with the vasomodulator action of this hormone on the renal vasculature. A significant increase in the fractional K⁺ excretion observed in the TPTX+Ca²⁺ group as compared with both control and TPTX, groups suggests that the excreted load of Ca²⁺ may interfere with tubular K⁺ handling in the absence of PTH. PTH (10^–6M) added to the bath of the isolated inner medullary collecting tubules did not change the osmotic permeability, of intact, TPTX, and TPTX+Ca²⁺ rats. Furthermore, it did not modify the antidiuretic hormone induced changes in the osmotic permeability. These results suggest that this segment of the nephron is PTH insensitive as far as water and ion transport are concerned.