Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.
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PMID:Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats. 142 16

Farr's assay using double-stranded (ds) DNA from E. coli is a most sensitive and specific method for the detection of anti ds-DNA antibodies in patients with systemic lupus erythematosus (SLE). Because of the lack of sufficient DNA antigens, however, final antibody titers were hardly determined when the sera contained antibodies titered more than 100U/ml (or more than 60 per cent by DNA binding activities). In such sera DNA binding activities were measured by using ds-DNA tracer adjusted final concentration of NaCl to 125 mM. Higher binding activities measured by high-salt tracer are obtained significantly in SLE patients groups with nephrotic syndrome, proteinuria, cast, renal failure, diffuse proliferative nephritis, low serum complement levels, anemia and/or low IgG/IgA levels compared with the patients who lacked these clinical findings. In contrast the patients with digital rash or cramp showed significantly lower high-salt binding activities. The patients with pleuropericarditis tended to have lower bindings. The non-lupus patients including MCTD also had lower levels. These clinical characteristics could not be evaluated by standard Farr's assay. High-salt bindings suggest the presence of high avidity antibodies and also partly may mean the high levels of low avidity antibodies. The application of high-salt binding activities, thus, is a useful tool for the evaluation of clinical characteristics of SLE patients who had high levels of anti ds-DNA antibodies by standard Farr's assay.
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PMID:[Reassessment of measurement of anti double-stranded DNA antibodies by Farr's assay using double-stranded DNA from E. coli and application of DNA binding Activities in high salt solution]. 144 79

The relative tissue distribution and toxicity of cadmium (Cd) and mercury (Hg) in the liver and kidneys of rats when the metals are administered as either inorganic salts or complexed with MT were studied. Male Sprague-Dawley rats were injected (i.v.) with Cd or Hg inorganic salt of chloride or in a complex of MT at a dose of 0.3 mg/kg body weight. The concentration of MT and metals in plasma and urine was monitored for 7 days, at the end of which the rats were killed. Injection of both HgCl2 and Hg-MT induced the synthesis of MT only in the kidney but not in the liver, whereas CdCl2 and Cd-MT injections induced MT synthesis in both liver and kidney, respectively. Plasma MT levels increased 3 days after CdCl2 but not after HgCl2 injection, suggesting that hepatic MT may be an important source of plasma MT under our experimental conditions. Renal toxicity was observed morphologically and by an increase in blood urea nitrogen, plasma creatinine, proteinuria in rats injected with Cd-MT and both forms of Hg. Urinary MT excretion was significantly elevated in Cd-MT injected rats compared with those injected with CdCl2. However, HgCl2 and Hg-MT injected rats showed no significant difference in urinary MT excretion. The magnitude in the renal accumulation of Hg is similar after the administration of Hg-MT or HgCl2, but our findings suggest that the site of epithelial injury may be different. Injury effects of Hg-MT localized mainly in the terminal portions of the proximal convoluted tubule and the initial portions of the proximal straight tubule whereas inorganic Hg caused necrosis in pars recta segments of the proximal tubule.
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PMID:Exogenous metallothionein and renal toxicity of cadmium and mercury in rats. 147 92

In the Dahl S rat (DS), salt induces systemic and glomerular capillary hypertension associated with progressive glomerulosclerosis, while Dahl R rats (DR) remain normotensive, without glomerular abnormalities. Studies in experimental models have suggested that hypercholesterolemia may play a role in the development of glomerulosclerosis; however, it is unclear whether hypercholesterolemia alone, in the absence of hypertension, can initiate injury. To answer this question we induced hypercholesterolemia in salt-supplemented DS (DSC) and DR (DRC) by feeding a high cholesterol (4%) chow. Control rats (DS, DR) received high-salt, normal cholesterol chow. After eight weeks, DS and DSC developed equivalent hypertension (161 +/- 3 vs. 153 +/- 3 mm Hg, respectively, P = NS), while DR and DRC remained normotensive (138 +/- 5 vs. 131 +/- 5 mm Hg, P = NS; P less than 0.05 vs. DS and DSC). Cholesterol fed rats developed marked and equivalent hypercholesterolemia compared to controls (DS vs. DSC, 71 +/- 3 vs. 289 +/- 91 mg/dl, P less than 0.05; DR vs. DRC, 52 +/- 2 vs. 327 +/- 54 mg/dl, P less than 0.05). Hypertensive rats (DS, DSC) developed worse proteinuria and glomerular injury than normotensive rats (DR, DRC), but hypercholesterolemia exacerbated proteinuria and glomerulosclerosis only in DSC and not in DRC. Proteinuria significantly correlated with serum cholesterol in hypertensive rats (DS, DSC, P less than 0.05), but not normotensive rats (DR, DRC, P = NS). Furthermore, DSC had increased renal vascular resistance compared to DS, while no differences were found between DRC and DR. Thus, in the Dahl rat, hypercholesterolemia alone does not initiate glomerular injury. In this model, hypercholesterolemia is a pathogenetic factor in glomerular injury only when it coexists with systemic hypertension.
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PMID:Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury. 161 39

Felodipine is a dihydropyridine calcium antagonist which lowers total peripheral resistance and blood pressure in doses which have no effect on cardiac conduction and contractility. It increases the urinary excretion of sodium and water due to decreased renal tubular reabsorption from the glomerular ultrafiltrate. This is observed at low doses which do not affect blood pressure, renal blood flow (RBF) or glomerular filtration rate (GFR). Felodipine decreases total renal vascular resistance and causes a transient increase in RBF in patients with normal RBF. In patients with low pretreatment values, RBF is increased during chronic treatment. Felodipine does not affect normal GFR. Thus filtration fraction may decrease. In patients with severe hypertension and reduced GFR, felodipine treatment results in good blood pressure control and increased GFR. In animal models of progressive renal disease due to hyperfiltration, felodipine has no negative effect on GFR, glomerulosclerosis or survival although proteinuria may increase. In salt-sensitive rats given high salt diet, resulting in hypertension, hypoperfused kidneys and progressive renal damage, felodipine treatment results in reduced blood pressure, increased RBF and GFR, and reduced proteinuria and glomerulosclerosis. In patients with previously refractory hypertension and progressive impairment of renal function, felodipine treatment results in good blood pressure control and a reduced rate of progression. In animals, felodipine limits the extent of renal damage after ischemia and reperfusion.
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PMID:Renal effects of felodipine--a review. 161 69

We designed experiments to reveal the antihypertensive properties of cicletanine, a novel antihypertensive drug, in Dahl salt-sensitive (Dahl-S) rats. Cicletanine (39 mg/kg body weight per day for 6 weeks) ameliorated the development of hypertension in Dahl-S rats fed a high-salt (4% NaCl) diet. This blood pressure reduction was associated with a decrease in heart weight and vascular wall thickness. Moreover, urinary prostacyclin (PGl2) excretion was increased with cicletanine treatment, being inversely related to systolic blood pressure. Proteinuria and urinary excretion of n-acetyl-beta-D-glucosaminidase were decreased and glomerular filtration rate was increased with this treatment. Morphological investigation revealed an improvement in glomerulosclerosis, renal tubular damage and intrarenal arterial injury in the salt-induced hypertensive rats. In contrast, trichloromethiazide, which decreased blood pressure to the same extent as cicletanine, lowered urinary PGl2 excretion and generally did not ameliorate the deteriorated renal functions and morphological abnormalities. Thus, these data indicate that cicletanine ameliorates the development of hypertension in Dahl-S rats and protects the cardiovascular and renal systems against the injuries seen in the hypertension. The enhanced vasodepressor PGl2 synthesis probably participates, to some extent, in these beneficial properties of long-term cicletanine treatment.
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PMID:Antihypertensive effects of cicletanine and renal protection in Dahl salt-sensitive rats. 165 82

Normal pregnancy is associated with increased levels of digitalis-like factor (DLF) and erythrocyte sodium-lithium countertransport (RBC CTT), which return to normal levels postpartum. Patients with pregnancy-induced hypertension (PIH) have greater increases in both factors than women with normotensive pregnancies. This study was designed to determine if both abnormalities are observed concomitantly in PIH, if they correlate with blood pressure, if they correlate negatively with a hormonal index of volume status (PRA), and if they differ in women with and without proteinuria. Twenty-six normotensive women and 26 women with PIH were studied in the third trimester. Thirteen of these patients were also studied 6 months postpartum. Women with PIH, compared to those who were normotensive, had higher RBC CTT (0.49 +/- 0.04 vs. 0.36 +/- 0.03 mmol Li/L cells.h; P = 0.004) and DLF (0.30 +/- 0.3 vs. 0.20 +/- 0.03 microgram digoxin equiv./L; P = 0.01) and lower PRA [4.58 +/- 0.76 vs. 7.34 +/- 0.86 ng/mL.h (1.27 +/- 0.21 vs. 2.04 +/- 0.24 ng/L.s); P = 0.001]. All three parameters correlated significantly with diastolic blood pressures (RBC CTT and DLF positively (P less than or equal to 0.02) and PRA negatively (P = 0.03). Comparisons of DLF, RBC CTT, and PRA demonstrated a significant correlation of RBC CTT and DLF for normotensive pregnant women only (r = 0.38; P = 0.05). Patients with PIH were further analyzed according to whether proteinuria (24-h urinary protein, greater than 0.30 g; urine dipstick, greater than or equal to 2+) was present or absent. There was no significant difference in diastolic blood pressure or PRA between the hypertensive subpopulations, although there was a tendency for those without proteinuria to have lower PRAs [3.85 +/- 0.80 ng/mL.h (1.07 +/- 0.02 ng/L.s)] than those with proteinuria [5.31 +/- 1.30 ng/mL.h (1.48 +/- 0.36 ng/L.s)]. RBC CTT was significantly higher (P less than 0.05) in women with PIH without proteinuria, whereas serum DLF was significantly higher in women with PIH with proteinuria (P less than 0.05). In 13 women studied 6 months postpartum, there was a significant reduction in serum DLF, RBC CTT, and PRA for all women and in blood pressure for women who had had PIH (P less than 0.01). Thus, women with PIH, compared to normotensive pregnant women, had abnormalities in a variety of factors known to be volume sensitive or indicative of salt- and volume-sensitive forms of hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Markers of sodium and volume homeostasis in pregnancy-induced hypertension. 172 15

To explore the role of systemic hematocrit in the vascular adaptations which characterize desoxycorticosterone-salt hypertension, studies were performed in three groups of rats with uninephrectomy, desoxycorticosterone administration, and 1% saline in the drinking water. One group received recombinant human erythropoietin to increase hematocrit, and another group was subjected to phlebotomy and fed a low-iron diet to induce anemia. Control rats exhibited systemic and glomerular capillary hypertension, proteinuria, and substantial glomerular sclerosis at 8 wk. Erythropoietin modestly increased hematocrit and blood pressure and substantially aggravated glomerular capillary pressure, proteinuria, and glomerular sclerosis. In contrast, reduction of hematocrit with a low-iron diet significantly attenuated systemic and glomerular hypertension, proteinuria, and sclerosis. It was concluded that the pace of progression of glomerular injury can be limited by chronic reduction in hematocrit, which effectively ameliorates both systemic and glomerular hypertension in this model of salt-sensitive hypertensive renal disease.
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PMID:Anemia ameliorates progressive renal injury in experimental DOCA-salt hypertension. 176 13

To establish if the benefit of angiotensin converting enzyme inhibitor therapy in retarding progressive diabetic renal injury is due to a specific intrarenal effect of the systemic hypotensive effect, we studied the effect of long-term ramipril treatment on blood pressure, glomerular filtration rate, and urinary protein excretion in streptozotocin-diabetic spontaneously hypertensive rats. The hypotensive effect of ramipril was prevented by a high salt diet, which did not alter the degree of renal angiotensin converting enzyme inhibition. Three weeks after uninephrectomy and induction of diabetes, rats were allocated to three groups. Groups 1 and 2 were given 1% NaCl, whereas group 3 was given water as drinking solution. One week later, groups 2 and 3 received 0.4 mg/kg/day ramipril in their drinking solution, which was continued over a 2-month period. Ramipril produced a blood pressure fall only in water-drinking rats (group 3) despite a similar reduction in plasma and renal angiotensin converting enzyme activity in groups 2 and 3. Salt-loaded rats had a progressive increase in urinary protein excretion over the duration of study. Ramipril treatment prevented an increase in protein excretion only in animals given water and with a reduced systolic blood pressure. Glomerular filtration rate was similar in all three groups. Ramipril treatment improved animal survival independently of a reduction in blood pressure or an effect on proteinuria. Although it is possible that angiotensin converting enzyme inhibitors have specific intrarenal effects reducing progression of diabetic proteinuria, concomitant control of systemic blood pressure appears to be necessary to demonstrate a benefit.
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PMID:Salt blocks the renal benefits of ramipril in diabetic hypertensive rats. 182 92

A number of studies based on animal models of both diabetes and renal insufficiency have shown that adequately reducing blood pressure attenuates the progression of glomerulosclerosis and decreases urinary protein excretion. Furthermore, compared with conventional antihypertensive therapy, angiotensin converting enzyme (ACE) inhibitors show a greater benefit in reducing these parameters. Nineteen published animal studies have investigated the effects of calcium antagonists on renal hemodynamics and glomerulosclerosis, but only three of them have evaluated the use of calcium antagonists with models of diabetes. Of six micropuncture studies based on a 1 5/6 nephrectomy model of renal insufficiency, five demonstrated reduced efferent arteriolar resistance, two showed reduced glomerular capillary pressure (PGC), and two showed significantly reduced proteinuria and glomerulosclerosis. Studies using nifedipine with both the unilaterally nephrectomized DOCA salt rat model and the 1 5/6 nephrectomy model demonstrated reduced proteinuria and glomerulosclerosis that was independent of reduced PGC. Two separate micropuncture studies of the spontaneously hypertensive rat model also found reduced efferent arteriolar resistance and PGC as well as proteinuria. Finally, studies of Dahl "salt-sensitive" rats showed an early decrease in glomerulosclerosis without a significant change in either proteinuria or glomerulosclerosis after five weeks. The results of eleven clinical studies of diabetic patients have been published; they showed divergent effects of calcium antagonists on renal function and urinary protein excretion. In the various animal models, the divergent renal hemodynamic and histologic effects reported for calcium antagonists may be largely due to the equality of blood pressure reduction, the varied baseline hemodynamic profiles, and the divergent status of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal effects of calcium antagonists in diabetes mellitus. An overview of studies in animal models and in humans. 191 Jun 42


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