摘要:

Inhibition of nitric oxide (NO) synthesis by structural analogues of L-arginine reduces glomerular filtration, renal blood flow, sodium excretion, and urine output. NG-nitro-L-arginine methyl ester (L-NAME) inhibits constitutive and inducible isoforms of NO synthase, while aminoguanidine (AG) selectively inhibits inducible isoforms of NO synthase. We assessed the NO-inhibitory activity of AG on renal function. Rats were treated with aminoguanidine 50 mg/kg daily for 2 months, followed by L-NAME (25 mg/kg/day) for 1 week to inhibit all NO synthase isoforms. After treatment with L-NAME, we performed baseline renal function measurements, then infused L-arginine (2.5 mg/l00 g BW×min) to reverse NO inhibition and assessed whether AG exerted NO-inhibitory activity independently of L-NAME. Prior to L-arginine infusion, AG-treated rats did not differ from controls with respect to body weight, kidney weight, systolic blood pressure, urine flow rate, urinary protein or albumin excretion, or urinary excretion of NO metabolites. After L-arginine infusion, all animals showed a 10-15% decrease in mean arterial blood pressure. L-Arginine-induced increases in urine flow, inulin clearance, PAH clearance, sodium excretion, and NO metabolite excretion were blunted in aminoguanidine-treated animals. To assess long-term effects of aminoguanidine, rats were treated for 12 months. Urinary excretion of NO metabolites was lower than controls. Inulin clearance was higher than controls. Aminoguanidine blunts the effect of L-ariginine on renal hemodynamics independently of the nitric oxide synthase inhibitor, L-NAME. However, the use of aminoguanidine for 12 months in rats did not adversely affect renal function

ISSN:1420-4096    

DOI:10.1159/000174148

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Cationic colloid gold, a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanions, including heparan sulfate protoglycan in genetic salt-sensitive (SBH/Y) and resistant (SBN/Y) hypertensive rats, with or without high dietary salt intake. GBM morphology, renal function and nitric oxide, as measured by plasma and urine nitrite (NO2) and nitrate (NO3) were also determined. In the salt-sensitive rats the high-salt dietary intake resulted in severe hypertension, proteinuria and decreased glomerular filtration rate. After 1 month of high-salt intake, the average width of the GBM of salt-sensitive rats was higher by 27% than that of salt-resistant rats. The number of GBM anionic sites (lamina rata externa and interna) was much lower in both salt-sensitive and salt-resistant groups after 1 month of salt loading, 8.04 ± 0.36 and 7.8 ± 0.25 counts/cm, respectively, compared to the respective values of non-salt-loaded animals, 20.58 ± 1.08 counts/cm in the SBH/Y (p < 0.001) and 21 ± 1.86 counts/cm in the SBN/Y (p < 0.001). A decreased nitric oxide production was found in the salt-sensitive rats before and after salt loading compared with the salt-resistant group. No correlation was found between the nitric oxide changes and the GBM modifications. It is concluded that high-salt intake may be deleterious to the permselectivity of the GBM. It is suggested that salt restriction in hypertension may have a beneficial effect in preventing GBM permselectivity changes and proteinu

ISSN:1420-4096    

DOI:10.1159/000174149

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

This study was designed to assess the renal capability to autoregulate total blood flow, glomerular filtration rate (GFR) and local GFR in outer, middle and inner cortical layers (OC, MC, IC) in the two-kidney, one-clip (2K-1C) renovascular hypertensive rat, with or without acute infusion of the angiotensin II receptor antagonist losartan (5 mg/kg, i.v.). Age-matched, sham-operated Wistar rats were used as controls. The hemodynamic study in all animals was performed 4 weeks after clipping. The clipping increased blood pressure significantly, whereas losartan reduced the renal arterial pressure (RAP) from 165 ± 8 to 125 ± 6 mm Hg (p < 0.01) in 2K-1C hypertensive rats and reduced the RAP from 107 ± 2 to 101 ± 1 mm Hg (p < 0.05) in normotensive animals. Renal blood flow (RBF), total and local GFR were decreased in the nonclipped kidney of 2K-1C hypertensive rats compared with sham-operated rats, but losartan significantly increased the RBF and GFR. RBF was well maintained in response to reduction in RAP in the nonclipped kidneys with and without losartan treatment. The capability of total GFR autoregulation was impaired in untreated 2K-1C hypertensive rats and losartan-treated sham-operated rats, whereas losartan completely abolished GFR autoregulation in the nonclipped kidney of 2K-1C hypertensive rats. Losartan impaired autoregulation of zonal GFR to the same extent in all three cortical layers of sham-operated rats, whereas in the nonclipped kidney of 2K-1C hypertensive rats losartan had a more pronounced effect on the superficial GFR autoregulation than in middle and inner cortex, indicating that angiotensin II plays a major role in regulating the GFR response to the acute changes of renal arterial press

ISSN:1420-4096    

DOI:10.1159/000174150

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Cleavage of the C-terminal tripeptide of angiotensin I (Ang I) by neutral endopeptidase 24.11 releases angiotensin 1-7 (Ang 1-7). Because Ang I and neutral endopeptidase 24.11 are present in proximal tubular fluid and brush border, respectively, Ang 1-7 could be released into proximal tubular fluid to affect nephron function. Therefore, we studied the effect of intratubular Ang 1-7 (10-12 to 10-8M) on nephron function employing in vivo renal micropuncture in inactin-anesthetized Munich-Wistar-Frömter rats. We observed that: (i) Intratubular application of Ang 1-7 for 3,15, or 30 min did not affect reabsorption in the microperfused proximal convoluted tubule determined as net fluid reabsorption. (ii) During perfusion of Henle’s loop for 15 min with artificial tubular fluid (time control), we observed a decline in fluid, potassium and sodium reabsorption by 20,18 and 5%, respectively. A similar decline in reabsorption was seen with intratubular application of Ang 1-7 in a concentration of 10-12 or 10-10M. In contrast, intratubular application of Ang 1-7 in a concentration of 10-8M increased fluid, potassium and sodium reabsorption in that nephron segment by 11, 9 and 3%, respectively. The latter response was completely abolished by ATI angiotensin II receptor antagonist losartan (10-6M). (iii) Intratubular application of Ang 1-7 did not affect net sodium, potassium, or fluid reabsorption in the distal tubule, (iv) TGF response assessed by measuring proximal tubular stop-flow pressure or single nephron filtration rate during orthograde open-loop perfusion of Henle’s loop was not significantly altered by intratubular application of Ang 1-7. These findings show that intratubular application of Ang 1-7 in concentrations which possibly cover the physiological range does not significantly alter (i) tubular reabsorption in proximal convoluted or distal tubule, or (ii) TGF response. Intratubular Ang 1-7 at a concentration of 10-8M appears to increase reabsorption in Henle’s loop by an ATI angiotensin II receptor-mediated mechanism, the physiological relevance of which remains to be estab

ISSN:1420-4096    

DOI:10.1159/000174151

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The tubular site of furosemide (F) action was studied by the technique of diuretic microinjection (MIJ) into proximal tubules of the rat nephron. F was injected into the last proximal superficial loop of 51 proximal tubules, at the concentration of 3 · 10-4 mol/l in an infusate that contained 14C-inulin. Collections were performed at the early distal tubule before and after MIJ. Single nephron filtration rate (SNGFR) remained unchanged, while the percent of filtered volume reabsorbed up to the site of collection was 85 ± 2 before, 79 ± 2% after MIJ, p < 0.005. The calculated concentration of F in the collected distal tubular fluid during the post-MIJ measurements averaged 3 · 10-5 0.6). The respective percent reabsorptions were 70 ± 3 and 73 ± 3% (p ± 0.3). In order to determine whether the technique per se was suitable to detect changes in reabsorption, the proximal MIJ study was repeated by using the carbonic anhydrase inhibitor dichlorphenamide 3 · 10-5 mol/l in the microinjectate: while SNGFR remained unchanged, percent reabsorption fell from 63+5 to 45 ± 7% during injection of the diuretic, p < 0.03. We conclude that the technique is adequate to examine the effects of drugs, and that F does not reduce proximal volume absorption at concentrations of 3 · 10-5 mol/l. The loop diuretic decreases distal volume absorption by abolishing the osmotic gradient between blood and tubular fluid along the early distal convol

ISSN:1420-4096    

DOI:10.1159/000174152

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The present investigation examined the possible influence of urinary calcium excretion on the concentration of renal calbindin-D28k. Thiazide diuretics stimulate calcium transport across the epithelial cells of the distal tubule, which express calbindin-D28k in high concentrations. Calbindin-D28k is assumed to facilitate transcellular Ca diffusion. Reduced urine calcium excretion and increased urine output were induced in Wistar rats by infusion of bendroflume-thiazide 1 mg/kg/day. The two control groups had infusions of either furosemide 20 mg/kg/day or vehicle, n = 8 in each group. Urinary Ca excretion was reduced to 10% in the thiazide group and increased by 50% in the furosemide group. Renal concentrations of calbindin-D28 showed no difference between vehicle, thiazide- and furosemide-treated rats. No differences in plasma concentrations of calcium, magnesium, phosphorus, urea, PTH, calcitonin and 1,25-(OH)2D were found between the groups. The present study describes that urine calcium excretion selectively can be manipulated without accompanying changes in renal calbindin-D28k concentrations. The data, therefore, suggest that urinary calcium excretion is not a significant determinator of cytosolic concentrations of renal calbindin-D28k.

ISSN:1420-4096    

DOI:10.1159/000174153

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Renal acid excretion and proximal and distal nephron acidification were evaluated 20 days after induction of diabetes, in rats, by intraperitoneal injection of streptozotocin (45 mg/kg). Titratable acidity in urine was measured by microtitration and ammonium excretion (NH+4) by spectrophotometry. Proximal tubular acidification was evaluated by the kinetics of reabsorption of perfused HCO-3 Distal nephron acidification was evaluated by measuring urine – blood pCO2 differences under alkaline overload. The net acid excretion (titratable acidity + NH+4-HCO-3) was higher (p < 0.001) in diabetic rats (9.82 ± 0.65 μmol/min/kg, n = 26) than in the control group (6.34 ± 0.14, n = 24). Proximal HCO-3 reabsorption was also higher (p < 0.001) in diabetic rats (8.38+0.11 nmol/cm2/s, n = 12) than in the control group (2.30 ± 0.10, n = 22); however, evaluation of distal nephron H+ secretion by urine – blood pCO2 methodology was similar in both groups. We concluded that in rats with induced diabetes mellitus there is an increased rate of proximal HCO-3 reabsorption, possibly effected by a higher density of Na+/H+ antiporter in the luminal membrane of the proximal tubule and by an increased proton-motive force of the H+ secretory mechanism. The higher rates of H+ secretion generate lower stationary proximal luminal pH and probably maintain the blood pH within the physiological range.

ISSN:1420-4096    

DOI:10.1159/000174154

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Cellular autophagy in the cells of distal tubular segments (DT cells) of the kidney cortex in streptozotocin-diabetic rats was evaluated by quantitative electron microscopy. Five days after streptozotocin administration, volume and numerical densities of autophagic vacuoles (AVs) in DT cells were reduced by 56 and 57%, respectively. The correction of the diabetic state by insulin injection reversed the inhibition of cellular autophagy. Volume and numerical densities of AVs increased by 97 and 53%, respectively. Endogenous insulin replacement by islet transplantation showed the same effect on cellular autophagy. Volume and numerical densities of AVs increased by 82 and 34%, respectively, as compared with sham-operated diabetic animals. The data show that, during diabetic kidney hypertrophy, the cellular autophagy is inhibited in DT cells to the same extent as in proximal tubular cells, suggesting that DT cells contribute in a balanced manner to hypertrophic growth of the kidney cortex. Similary, DT cells are involved in the catabolic reaction, i.e., stimulation of autophagy, after metabolic correction of the diabetic state by insulin.

ISSN:1420-4096    

DOI:10.1159/000174155

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Rabbit renal proximal tubular cells, cultured to confluency on a permeable collagen film in a two-chamber system, were exposed for 72 h to various concentrations of the nephrotoxic antibiotic, cephaloridine (CLD). A decrease in cellular proteins, leakage of lactate dehydrogenase and morphological changes appeared at CLD concentrations of 0.1,1.0, and 0.5 mg/ml, respectively. The permeability of the monolayer to Lucifer yellow (LY), a dye that does not cross cell membranes, was increased by 1 or 2 mg/ml but not by lower concentrations of CLD. The large basolateral/apical glucose concentration gradient established by the cells was decreased by CLD. However, the fact that, at the CLD concentration of 1 mg/ml, LY totally equilibrated by diffusion across the monolayer, whereas the injured monolayer was still able to maintain a detectable glucose gradient, shows that damage caused by CLD to the diffusion barrier prevails over that affecting glucose uptake. Consistent with the data in the literature concerning the mechanism of CLD accumulation in renal cells, our results show that CLD was more toxic when it was added at the basolateral than at the apical side of the cultured cells. These results illustrate the advantages of using a two-chamber system of cell culture in nephrotoxicity studies.

ISSN:1420-4096    

DOI:10.1159/000174156

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Human envenomation caused by bee or wasp stings has been reported to cause acute renal failure (ARF), usually due to acute tubular necrosis (ATN), as a frequent complication. The pathogenetic mechanisms of ATN occurring in these accidents are still unclear. In the present study, female Wistar rats weighing 150-200 g were injected intravenously with Africanized bee venom at a dose of 0.4 µl/l00 g body weight and used in functional and light microscopy studies. The animals were divided into two groups: the early group was studied 3-8 h after inoculation, and the late group was studied 24-30 h thereafter. The animals showed ARF characterized by reduction of glomerular filtration rate with increasing levels of plasma creatinine. They also showed increased fractional sodium and potassium excretions, suggesting changes in the proximal portion of the nephron. The water transport through collecting tubules was reduced, with consequent diuresis, indicating functional changes in the distal portion of the nephron. These functional changes were more marked in the early group, with recovery tending to occur after 24 h. Albuminuria was also observed in this group. Light microscopy showed ATN mainly in cortex and outer medulla, with isolated necrosis in cells or small groups of cells and cast formation in the distal and collecting tubules. After 24 h frequent mitotic figures were found in the tubular epithelium. The observed ARF was due to ATN which in turn was probably caused by multiple effects, mainly hemodynamic changes secondary to cardiotoxicity and systemic vasodilation caused by the venom, myohemoglobinuria, and the direct action of the venom on tubular cells

ISSN:1420-4096    

DOI:10.1159/000174157

出版商:S. Karger AG    

年代:1997

数据来源: Karger