Cytokine profiles in women with different subtypes of major depressive disorder.

BACKGROUND: Depression has been associated with activation of the immune system. Some studies have shown increased levels of pro-inflammatory cytokines in patients with major depressive disorder (MDD), but conflicting results also have been described. METHODS: Forty-six unmedicated women with MDD were classified in subgroups (melancholic vs. non-melancholic; acute vs. chronic; severe vs. moderate, and episodic vs. recurrent presentations) and compared with 41 healthy controls. Evaluations of serum IL-1beta, IL-6, IFN-gamma and cortisol were performed on both groups. Patients were evaluated prior and after antidepressant treatment. RESULTS: The sub-classification of depression did not predict differences in cytokine levels. Patients currently depressed had similar levels of cytokines and cortisol as healthy controls. After remission of the symptoms, patients with MDD evolved with enhancement of cytokine levels, but no differences were observed in cortisol levels. LIMITATIONS: In patient treatment, two different classes of antidepressants were applied. The dexamethasone/CRH test was not performed to evaluate the HPA axis. CONCLUSIONS: Out-patient women diagnosed with MDD exhibited normal levels of both cortisol and cytokines before treatment, yet demonstrated an increase in cytokines after antidepressant treatment. In some patients with MDD, the presence of acute stress due to hospitalization may indeed contribute and justify the usual finding of higher levels in both cortisol and cytokines.

Genetic potential for an acute inflammatory response in IgA glomerulonephritis in mice

Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 ± 0.4 vs 0.3 ± 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 ± 0.3 vs 1.1 ± 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.

Genetic potential for an acute inflammatory response in IgA glomerulonephritis in mice.

Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 +/- 0.4 vs 0.3 +/- 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 +/- 0.3 vs 1.1 +/- 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.

Nephrotoxicity of Bence-Jones proteins: interference in renal epithelial cell acidification.

The aim of the present study was to evaluate the acidification of the endosome-lysosome system of renal epithelial cells after endocytosis of two human immunoglobulin lambda light chains (Bence-Jones proteins, BJP) obtained from patients with multiple myeloma. Renal epithelial cell handling of two BJP (neutral and acidic BJP) was evaluated by rhodamine fluorescence. Renal cells (MDCK) were maintained in culture and, when confluent, were incubated with rhodamine-labeled BJP for different periods of time. Photos were obtained with a fluorescence microscope (Axiolab-Zeiss). Labeling density was determined on slides with a densitometer (Shimadzu Dual-Wavelength Flying-Spot Scanner CS9000). Endocytosis of neutral and acidic BJP was correlated with acidic intracellular compartment distribution using acridine orange labeling. We compared the pattern of distribution after incubation of native neutral and acidic BJP and after complete deglycosylation of BJP by periodate oxidation. The subsequent alteration of pI converted neutral BJP to acidic BJP. There was a significant accumulation of neutral BJP in endocytic structures, reduced lysosomal acidification, and a diffuse pattern of acidification. This pattern was reversed after total deglycosylation and subsequent alteration of the pI to an acidic BJP. We conclude that the physicochemical characteristics of BJP interfere with intracellular acidification, possibly explaining the strong nephrotoxicity of neutral BJP. Lysosomal acidification is fundamental for adequate protein processing and catabolism.

Nephrotoxicity of Bence-Jones proteins: interference in renal epithelial cell acidification

The aim of the present study was to evaluate the acidification of the endosome-lysosome system of renal epithelial cells after endocytosis of two human immunoglobulin lambda light chains (Bence-Jones proteins, BJP) obtained from patients with multiple myeloma. Renal epithelial cell handling of two BJP (neutral and acidic BJP) was evaluated by rhodamine fluorescence. Renal cells (MDCK) were maintained in culture and, when confluent, were incubated with rhodamine-labeled BJP for different periods of time. Photos were obtained with a fluorescence microscope (Axiolab-Zeiss). Labeling density was determined on slides with a densitometer (Shimadzu Dual-Wavelength Flying-Spot Scanner CS9000). Endocytosis of neutral and acidic BJP was correlated with acidic intracellular compartment distribution using acridine orange labeling. We compared the pattern of distribution after incubation of native neutral and acidic BJP and after complete deglycosylation of BJP by periodate oxidation. The subsequent alteration of pI converted neutral BJP to acidic BJP. There was a significant accumulation of neutral BJP in endocytic structures, reduced lysosomal acidification, and a diffuse pattern of acidification. This pattern was reversed after total deglycosylation and subsequent alteration of the pI to an acidic BJP. We conclude that the physicochemical characteristics of BJP interfere with intracellular acidification, possibly explaining the strong nephrotoxicity of neutral BJP. Lysosomal acidification is fundamental for adequate protein processing and catabolism

Mechanisms of albuminuria in the chronic nitric oxide inhibition model.

Chronic nitric oxide (NO) inhibition causes hypertension and renal injury. Concomitant salt overload promotes massive albuminuria. We investigated the mechanisms whereby these treatments impair glomerular permselectivity. Adult male Munich-Wistar rats received either a standard-salt (SS; 0.5% Na) or high-salt (HS; 3.1% Na) diet and either no treatment or the NO inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). At 30 days, albuminuria was moderate, the density of fixed anionic sites at the glomerular basement membrane (GBM), estimated by cationic ferritin binding, declined by approximately 35%, and the fractional clearance of 70-kDa neutral dextran (phi) rose moderately in rats receiving L-NAME and SS. Rats given L-NAME and HS exhibited massive albuminuria, whereas phi was nearly tripled. Depletion of GBM anionic sites was also seen in these rats. The GBM was thickened in both L-NAME-treated groups. These abnormalities were largely reversed after cessation of treatments. These results indicate that chronic L-NAME treatment promotes reversible albuminuria by impairing both glomerular size and charge selectivity. These effects likely reflect functional rather than structural disruption of the glomerular wall.

Defective proximal tubule lysosomal acidification by Bence Jones proteins. An immunoelectron microscopy study.

Proximal tubule handling of two human Bence Jones proteins (neutral and acidic BJP) was evaluated using protein A-gold labelling. After 30 min of acute light-chain infusion into 6 rats (alone or in combination with dinitrophenyl-aminopropyl-methylamine [DAMP]), kidney biopsies were processed for immunoelectron microscopy. Antibodies directed at monoclonal lambda light chains, mannose-6-phosphate cation-independent receptor (MPR) and DAMP were used. Labelling density (number of pA-gold particles/micrometer2), expressed as median (25-75 percentiles), differed (p < 0.05) between the two BJP, being 94.5 (32.9-212.5) vs. 19.4 (3.7-45.6) pA-gold/ micrometer2++ in endocytic vacuoles, and 297.3 (207.1-382.1) vs. 83.2 (16. 6-197.0) pA-gold/ micrometer2 in non-vacuolar electrondense endosome-lysosome structures. Labelling density for MPR was 47.7 (22. 2-84.6) vs. 4.0 (2.7-6.3) pA-gold/micrometer2. The area of MPR-labelled structures was also different, i.e.: 0.2 (0.1-0.4) vs. 0.9 (0.5-1.8) micrometer2. The endosome-lysosome pH distribution range differed significantly: 6.8 (6.4-7.0) vs. 6.3 (5.8-7.0). There was a significant accumulation of neutral BJP in endocytic structures, an acidification deficit of pre-lysosomes/lysosomes and MPR retention, suggestive of defective receptor recycling with this BJP. Interference with the physiological process of lysosomal acidification may be an important mechanism of higher nephrotoxicity in some BJP.

The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats.

The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after i.v. administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P < 0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P < 0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity.

The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats

The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after iv administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4 per cent) P<0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6 per cent) (P<0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4 per cent in the liver and 17.3 vs 18.6 per cent in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to diffedential tissue accumulation and possible toxicity.

Reduced humoral immunity in uremic mice genetically selected for high antibody response.

Biozzi's Selection IV-A mice, genetically selected for 25 generations for high and low antibody response to sheep red blood cells (SRBC), 2-3 months old, were made uremic by subtotal nephrectomy and characterized for antibody production against the selection antigen. T cell activity was evaluated in vitro by lymphocyte proliferation and interleukin 2 (IL 2) production in response to the super antigen staphylococcal enterotoxin B (SEB). Total and IgM antibody titers (log2) were similar in uremic and non-uremic low responder mice (total antibody: 4.0 +/- 0.6 vs 3.6 +/- 0.6; IgG: 3.0 +/- 0.7 vs 2.4 +/- 0.4), while uremic high responders presented with non-uremic animals (total antibody: 10.8 +/- 1.6 vs 13.0 +/- 0.2; IgG: 10.3 +/- 1.5 vs 11.7 +/- 0.3). T cell proliferation and IL 2 production were similar in uremic and non-uremic groups after SEB stimulation. The results indicate a genetic effect on sensitivity to humoral immune response modulation by uremic status, with deficient antibody production despite a normal T cell proliferative response to mitogen stimulation in short-duration renal failure in high responder mice.

Reduced humoral immunity in uremic mice genetically selected for high antibody response

Biozzi's Selection IV-A mice, genetically selected for 25 generations for high and low antibody response to sheep red blood cells (SRBC), 2-3 months old, were made uremic by subtotal nephrectomy and characterized for antibody production against the selection antigen. T cell activity was evaluated in vitro by lymphocyte proliferation and interleukin 2 (IL 2) production in response to the superantigen staphylococcal enterotoxin B (SEB). Total and IgM antibody titers (log2) were similar in uremic and non-uremic low responder mice (total antobody: 4.0 +/- 0.6 vs 3.6 +/- 0.6; IgG: 3.0 +/- 0.7 vs 2.4 +/- 0,4), while uremic high responders presented a blunted humoral immune response to SRBC when compared with non-uremic animals (total antibody: 10.8 +/- 1.6 vs 13.0 +/- 0.2; IgG: 10.3 +/- 1.5 vs 11.7 +/- 0.3). T cell proliferation and IL 2 production were similar in uremic and ...

[The effect of the complement system on the acute reversible rejection of kidney transplants]. / Zur Bedeutung des Komplementsystems für die akute reversible Abstossungsreaktion von Nierentransplantaten.

Although the involvement of complement in hyperacute renal allograft rejection is well established, its possible implication in acute reversible and chronic graft rejection remains uncertain. In recent clinical studies with a total of 83 patients undergoing renal transplantation, plasma levels of complement activation products were elevated 4-7 days before clinical diagnosis of graft rejection. Immunohistochemical analysis of biopsies revealed local complement activation with glomerular deposition of the terminal C5b-9 complex within 1 h after organ reperfusion. Increasing levels of complement activation products, preceding the clinical manifestation of renal graft rejections may be of diagnostic value in recognizing patients at risk.

Nephrotoxicity of human Bence Jones protein in rats: proteinuria and enzymuria profile.

The effect of intravenous administration of 80 mg purified human Bence Jones protein twice weekly for 5 weeks was investigated in male Wistar rats (N = 7; 2 months old). A state of immunological tolerance was demonstrated by the absence of a B-cell response (plaque-forming cells and hemagglutination titers) and by the absence of detectable antigen or antibody deposition in glomeruli, as indicated by light and electron microscopy. No rise in blood urea level was detected (33.9 +/- 4.3 vs 32.8 +/- 1.3 mg%). There was an increase in proteinuria (5.3 +/- 0.9 vs 32.8 +/- 4.0 mg/day), mainly due to Bence Jones protein excretion (0 vs 29.2 +/- 5.2 mg/day), with a slight but significant increase in albuminuria (0.2 +/- 0.1 vs 1.0 +/- 0.2 mg/day). There was a significant increase of lysosomal N-acetyl-beta-D-glucosaminidase in the urine (6.1 +/- 1.3 vs 72.7 +/- 18.8 mU/mg in creatinine). Lysosomal accumulation of Bence Jones protein in proximal tubular cells was evidenced by immunoelectronmicroscopy with protein A-gold. These results clearly showed proximal tubular dysfunction induced by chronic Bence Jones protein administration, without interference of autologous immune response as demonstrated by immunological state of tolerance.

Nephrotoxicity of human Bence Jones protein in rats: proteinuria and enzymuria profile

The effect of intravenous administration of 80 mg purified human Bence Jones protein twice weekly for 5 weeks was investigated in male Wistar rats (N = 7; 2 months old). A state of immunological tolerance was demonstrated by the absence of a B-cell response (plaque-forming cells and hemagglutination titers) and by the absence of detectable antigen or antibody deposition in glomeruli, as indicated by light and electron microscopy. No rise in blood urea level was detected (33.9 +/- 4.3 vs 32.8 +/- 1.3 mg per cent ). There was an increase in proteinuria (5.3 +/- 0.9 vs 32.8 +/- 4.0 mg/day), mainly due to Bence Jones protein excretion (0 vs 29.2 +/- 5.2 mg/day), with a slight but significant increase in albuminuria (0.2 +/- 0.1 vs 1.0 +/- 0.2 mg/day). There was a significant increase of lysosomal N-acetyl-beta-D-glucosaminidase in the urine (6.1 +/- 1.3 vs 72.7 +/- 18.8 mU/mg in creatinine). Lysosomal accumulation of Bence Jones protein in proximal tubular cells was evidenced by immunoelectronmicroscopy with protein A-gold. These results clearly showed proximal tubular dysfunction induced by chronic Bence Jones protein administration, without interference of autologous immune response as demonstrated by immunological state of tolerance

Snakebite-induced acute renal failure: an experimental model.

Acute renal failure (ARF) has been frequently reported after bites from the Viperidae snake family. The lack of a reproducible animal model has hampered the study of renal damage mechanisms. Intravenous injection of rats with 0.4 mg/kg of Bothrops jararaca venom produced functional and morphologic changes similar to those observed in human snakebite-induced ARF. There was an acute and significant decrease in the glomerular filtration rate, diuresis, and renal plasma flow. Serum fibrinogen levels decreased significantly. There was intravascular hemolysis, as shown by a significant decrease in hematocrit, and an increase in plasma lactate dehydrogenase levels and free hemoglobin. Blood pressure and serum creatine phosphokinase levels were not affected. Light and electron microscopy showed massive fibrin deposition in glomerular capillaries, proximal and distal tubular necrosis, and hemolyzed red blood cell casts in renal tubules. Based on these findings, a model of snakebite-induced ARF was achieved. Ischemia related to glomerular coagulation and intravascular hemolysis were the most important pathogenic factors causing a decrease in the glomerular filtration rate, although a direct venom nephrotoxicity cannot be excluded.

Influence of the hydrostatic intraperitoneal pressure and the cardiac function on the lymphatic absorption rate of the peritoneal cavity in CAPD.

The purpose of this study was to determine the influence of hydrostatic intraperitoneal pressure (IPP) and cardiac function (CF) on the lymphatic absorption rate (LAR) in 9 patients on continuous ambulatory peritoneal dialysis (CAPD). The LAR was measured by estimation of the intraperitoneal disappearance of dextran 70 added to 2 L of 2.5% dextrose dialysis solution. The patients remained in the supine position during the 4-hour dwell. The IPP was obtained by measuring a column of dialysate in the peritoneal dialysis line, immediately before the drainage of the peritoneal cavity. The pressure was measured at the level of the umbilical cicatrix with point zero located on the mid axillary line of the patient. IPP was measured at inspiration and expiration, and the average of these two measurements was taken. These patients also underwent an echocardiographic examination. The LAR was 0.46 +/- 0.25 mL/minute, and the IPP was 13.07 +/- 2.61 cm H2O. The IPP correlated positively with the LAR (r = 0.80, p < 0.05). The intraperitoneal volume at the 4-hour dwell correlated inversely with the IPP (r = -0.68, p < 0.05). The left ventricular circumferential shortened fraction was 36 +/- 6% (27%-43%) and did not correlate with the LAR. These data suggest that the LAR is higher in patients with more elevated IPP. In addition, the CF, in the range studied, does not affect the lymphatic absorption rate.

Influence of spontaneous contractions of the lymphatic vessels on the lymphatic absorption rate of the peritoneal cavity in CAPD.

The lymphatic vessels have sympathetic innervation. Noradrenaline increases the number of spontaneous contractions of the lymphatic vessels, whereas isoprenaline slows these contractions. The purpose of this study was to analyze the influence of the blockade of spontaneous contractions of the lymphatic vessels on the lymphatic absorption rate (LAR) in 6 patients on continuous ambulatory peritoneal dialysis (CAPD) by using 0.12 mg of isoprenaline added to 2 L of 2.5% dextrose dialysis solution. This dose of isoprenaline has been shown to inhibit bovine mesenteric lymphatic contractions. The LAR was measured by the quantification of the intraperitoneal disappearance of dextran 70 added to this same dialysis solution during a 4-hour dwell. All patients were submitted to a control test without isoprenaline. The LAR was 0.57 +/- 0.19 and 0.65 +/- 0.38 mL/minute (p > 0.05), with and without isoprenaline, respectively. We conclude that spontaneous contractions of the lymphatic vessels do not play an important role in the lymphatic drainage mechanism of the peritoneal cavity. The diaphragmatic contractions seem to be more important, since drugs that interfere with such diaphragmatic mechanisms alter the LAR.

Use of dextran 70 to estimate peritoneal lymphatic absorption rate in CAPD.

Peritoneal lymphatic absorption rate (LAR) in 15 patients on a CAPD program was measured by estimation of the disappearance of dextran 70 from the peritoneal cavity. The LAR was 1.03 +/- 0.45 ml/min. The cumulative lymphatic absorption, cumulative net transcapillary ultrafiltration, calculated net ultrafiltration (CUF) and measured net ultrafiltration (MUF) at 4 h exchange were respectively: 261 +/- 127 ml, 694 +/- 134 ml, 446 +/- 135 ml and 409 +/- 136 ml. Calculated and measured net ultrafiltration didn't differ significantly. An inverse correlation between MUF and LAR and a positive correlation between MUF and the ratio for dialysate glucose concentration at 4 hand dialysate glucose at 0 h (G4/G0) were observed (r = -0.522 and 0.547, respectively, p < 0.05). The multiple correlation coefficient between the MUF and LAR plus G4/G0 was higher (r = 0.617, p < 0.05). Peritonitis and the presence of diabetes didn't interfere with LAR. We have concluded that lymphatic absorption plus peritoneal transfer rate of glucose are important determinants of intraperitoneal volumes and that dextran 70 is a useful marker to measure lymphatic absorption.

Nephritis blunts urinary kallikrein excretion and aggravates DOCA/NaCl hypertension in rats.

1. Normal rats and passive Heymann membranous glomerulonephritic rats were chronically treated with DOCA/NaCl for 9 weeks. Normal and untreated nephritic rats were used as controls. Urinary kallikrein excretion (UKE), proteinuria and tail blood pressure (BP) were determined in awake rats. Glomerular filtration rate (GFR), plasma renin activity (PRA), and plasma potassium (PK) concentration were measured at the end of the experiment. 2. Comparison between basal and 9th-week measurements indicated that DOCA/NaCl administration significantly increased (P less than 0.05) UKE (3.96 +/- 0.30 vs 7.60 +/- 1.51 U/24 h) and BP (118 +/- 2 vs 135 +/- 6 mmHg) in normal rats, whereas in nephritic DOCA/NaCl-treated rats, UKE was unaltered (3.80 +/- 0.50 vs 3.40 +/- 0.30 U/24 h) and BP increased to higher levels (117 +/- 2 vs 152 +/- 3 mmHg) than in the normal DOCA/NaCl group (P less than 0.05). Passive Heymann nephritis alone did not affect UKE (3.56 +/- 0.40 vs 3.60 +/- 0.80 U/24 h) or BP (124 +/- 2 vs 125 +/- 2 mmHg). 3. At the end of the study, PK was decreased and PRA totally suppressed in both normal and nephritic DOCA/NaCl-treated rats. Proteinuria was more pronounced in nephritic DOCA/NaCl-treated rats (44.8 +/- 5.2 mg/day) than in control nephritic animals (15.1 +/- 2.4 mg/day) and GFR was increased equally in both DOCA/NaCl-treated groups. 4. The failure of nephritic rats to respond to DOCA/NaCl by increasing UKE was not associated with any significant derangement of renal function or structure and may have been related to the aggravation of arterial hypertension in this group.

Nephritis blunts urinary kallikrein excretion and aggravates DOCA/NaCl hypertension in rats

1. Normal rats and passive Heymann membranous glomerulonephritic rats were chronically treated with DOCA/NaCl for 9 weeks. Normal and untreated nephritic rats were used as controls. Urinary kallikrein excretion (UKE), proteinuria and tail blood pressure (BP) were determined in awake rats. Glomuerular filtration rate (GFR), plasma renin activity (PRA), and plasma potassium (PK) concentration were measured at the end of the experiment. 2. Comparasion between basal and 9th-week measurements indicated that DOCA/NaCl administration significantly increased (P < 0.05) UKE (3.96 ñ 0.30 vs 7.60 ñ 1.51 U/24 h) and 118 ñ 2 vs 135 ñ 6 mmHg) in normal rats, whereas in nephritic DOCA/NaCl-treated rats, UKE was unaltered (3.80 ñ 0.50 vs 3.40 ñ 0.30 U/24 h) and BP increased to higher levels (117 ñ 2 vs 152 ñ 3 mmHg) than in the normal DOCA/NaCl group (P < 0.05). Passive Heymann nephritis alone did not affect UKE (3.56 ñ 0.40 vs 3.60 ñ 0.80 /24 h) or BP (124 ñ 2 vs 125 ñ 2 mmØg). At the end of the study, PK was decrease and PRA totally suppressed in both normal and nephritic DOCA/NaCl - treated rats. Proteinuria was more pronounced in nephritic DOCA/NaCl - treated rats (44.8 ñ 5.2 mg/day) than in control nephritic animals (15.1 ñ 2.4 mg/day) and GFR was increased equally in both DOCA/NaCl-treated groups. 4. The failure of nephritic rats respond to DOCA/NaCl by increasing UKE was not associated with any significant derangement of renal function or structure and may have been related to the aggravation of arterial hypertension in this group