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)

The effects of long-term oral administration of losartan on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SPs) during the treatment period (5-20 weeks of age) and up to 8 weeks thereafter. Two doses of losartan, 1 and 10 mg/kg/day, were investigated, which afforded no and only moderate antihypertensive effects, respectively. During the treatment period, losartan at both doses completely suppressed stroke and mortality and strongly opposed (low dose) or abolished (high dose) the increases in saline intake, diuresis, and proteinuria observed in controls. It markedly limited (low dose) or abolished (high dose) vascular fibrinoid necrosis formation in the brain, kidneys, and heart. Finally, losartan, especially at the high dose, reduced arterial thickening and glomerular and tubulo-interstitial lesions in the kidneys, as well as arterial thickening, infarction, and fibrosis in the heart. Eight weeks after treatment discontinuation, all animals but one (low dose) were still alive. Vascular fibrinoid necrosis development remained strongly prevented (low dose) or fully suppressed (high dose) in all investigated organs. Finally, cardiac and renal lesions tended to worsen, and proteinuria was noted only in the low-dose group. We conclude that in SHR-SPs, angiotensin II, through AT1 receptor stimulation, most likely plays a major role in fibrinoid necrosis formation, vascular proliferative changes, and stroke occurrence and that losartan, most likely independently of its effect on blood pressure, affords a full and long-lasting protection against stroke and mortality both during and after the treatment period.
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PMID:Losartan's protective effects in stroke-prone spontaneously hypertensive rats persist durably after treatment withdrawal. 769 74

Glomerular epithelial cell injury is thought to be the primary reason for the development of proteinuria in puromycin aminonucleoside nephrosis (PAN), the rat model of nephrotic syndrome. By comparison mesangial cells are considered resistant to the effects of puromycin. The purpose of the present study was to investigate whether puromycin in non cytotoxic concentrations caused mesangial cell dysfunction, with particular reference to cell-extracellular matrix interactions. Mesangial cells, when embedded in collagen gels, contact after exposure to minimal essential medium (MEM) containing fetal bovine serum (FBS). This contractility, measured by determining changes in area of the collagen gel, is inhibited by puromycin in a dose dependent manner from 2.5 micrograms/ml to 160 micrograms/ml. At these concentrations there is no alteration of cell viability as measured by the tetrazolium salt (MTT) method and trypan blue exclusion. Immunocytochemistry with rhodamine phalloidin reveals that actin filaments are not disrupted. The antioxidants, superoxide dismutase (SOD) and catalase as well as diphenylene iodonium (DPI), a flavoprotein inhibitor, not only counteracted the effect of puromycin on gel contraction, but also enhanced gel contraction when added to mesangial cells on their own. Aminotriazole, an inhibitor of endogenous catalase, inhibited mesangial cell-induced gel contraction in a dose dependent manner (5 mM to 40 mM), and this effect was completely reversed by addition of catalase. Mesangial cells preloaded with dihydrorhodamine and exposed to puromycin (5 micrograms/ml to 160 micrograms/ml) exhibited a dose dependent increase in rhodamine 123 fluorescence, indicating production of reactive oxygen species (ROS). This effect was blocked by the addition of DPI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Puromycin aminonucleoside inhibits mesangial cell-induced contraction of collagen gels by stimulating production of reactive oxygen species. 775 81

Wistar rats with surgically removed 5/6 of renal parenchyma were fed either standard (0.35% salt content) or a high-salt (2%) diet. Half of the animals of each group drunk plain water while the other half was provided water enriched with the angiotensin-converting enzyme inhibitor enalapril (ENA) at a dose of 5 mg/kg/day. In rats receiving standard diet, ENA had a significant inhibitory effect on the consequences of ablation: the rats had normal blood pressure, low proteinuria, and high endogenous creatinine clearance compared to water-drinking controls. The high-salt diet significantly enhanced the sequelae of ablation: a high blood pressure and proteinuria, low clearance, which ENA was unable to prevent in these animals. No plausible explanation for the absence of ENA's beneficial effect is available: one can speculate that, under conditions of high-salt intake, the activity of the renin-angiotensin system is suppressed leaving no place for ENA to exert its effect. We also believe that the highly adverse effect of a high-salt diet in chronic renal failure is due to growth factors other than angiotensin II.
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PMID:[Ineffectiveness of ACE inhibitors (enalapril) on glomerular damage in rats after a 5/6 nephrectomy and a high-salt diet]. 776 86

Oral calcium supplementation is reported to have phosphate-binding and antihypertensive effects. Since both phosphate binders and antihypertensive agents are reported to attenuate renal injury, we studied the effect of oral calcium carbonate (CaCO3) administration on the course of renal deterioration using doxorubicin-induced renal failure in rats treated with deoxycorticosterone acetate and salt for 10 weeks. Rats were divided into four groups: the CaCO3 (6.0 g/kg/d) group (n = 12), the aluminum hydroxide (Al(OH)3; 6.0 g/kg/d) group (n = 11, as a phosphate-binder control), the hydralazine (10 mg/kg/d) group (n = 11, as an antihypertensive control), and the control group (n = 12). All agents were given as a mixed chow diet. Blood pressure and urinary protein excretion progressively increased in the control rats. CaCO3 and hydralazine lowered blood pressure, but Al(OH)3 did not (185 +/- 4 mm Hg, control; 160 +/- 5 mm Hg, CaCO3; 171 +/- 8 mm Hg, Al(OH)3; 156 +/- 5 mm Hg, hydralazine at week 10). Proteinuria was reduced in the rats treated with CaCO3 and Al(OH)3 compared with those without the treatment (986 +/- 86 mg/d, control; 551 +/- 54 mg/d, CaCO3; 527 +/- 31 mg/d, Al(OH)3; and 955 +/- 68 mg/d, hydralazine at week 10). Serum phosphate concentration and calcium phosphate products also were significantly lower in both the CaCO3 and Al(OH)3 groups than in the control group. At week 10, increased serum urea nitrogen, impaired renal function, and glomerular sclerosis present in the control group were significantly attenuated in both in the CaCO3 and Al(OH)3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oral calcium carbonate administration ameliorates the progression of renal failure in rats with hypertension. 777 88

Chloroanilines are widely used chemical intermediates for the manufacture of dyes, agricultural chemicals and industrial compounds. Nephrotoxicity occurs as one toxicity following intraperitoneal (i.p.) administration of chloroaniline hydrochlorides to rats. The purpose of this study was to examine the effect of chemical form, route of administration and vehicle on 3,5-dichloroaniline-induced nephrotoxicity. In one set of studies, male Fischer 344 rats (four to eight per group) were administered a single i.p. injection of 3,5-dichloroaniline free base or hydrochloride salt, cysteine hydrochloride or ornithine hydrochloride (0.8, 1.0 or 1.5 mmol kg-1) or an appropriate vehicle and renal function monitored for 48 h. Only 3,5-dichloroaniline hydrochloride induced nephrotoxicity that was characterized as acute renal failure. When 3,5-dichloroaniline free base (0.8 mmol kg-1) was administered in dimethyl sulfoxide (DMSO), all rats died within 24 h. In a second experiment, the free base or hydrochloride form of 3,5-dichloroaniline (1.5 mmol kg-1) or vehicle (0.9% saline or sesame oil, respectively) were administered orally and renal function monitored for 48 h. No evidence of nephrotoxicity was observed following either treatment. However, when the hydrochloride salt was given in 25% DMSO in 0.9% saline, all rats died within 24 h, with two rats demonstrating increased proteinuria, glucosuria and hematuria within the first 6 h after treatment. These results demonstrate that 3,5-dichloroaniline nephrotoxicity is potentiated by the administration of systemic acid, but that acid alone has no effect on renal function at the dose tested. Also, 3,5-dichloroaniline (hydrochloride or free base form) is less toxic orally than when administered i.p.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of chemical form, route of administration and vehicle on 3,5-dichloroaniline-induced nephrotoxicity in the Fischer 344 rat. 788 46

Angiotensin II (AII) appears essential in remnant kidney models of renal injury in rats, and renal injury was reduced by angiotensin-converting enzyme inhibitor (ACEI). To determine whether this is due to AII blockade or other actions of ACEI, we studied a nonpeptide AII type 1 receptor antagonist and an ACEI in partially nephrectomised spontaneously hypertensive rats (SHR). Thirty SHR underwent surgery and were divided into three equal groups: Control, TCV (0.5 mg/kg/day TCV-116), and CAP (30 mg/kg/day captopril). All SHR received a 5%-NaCl diet. Systolic blood pressure (SBP) and urinary protein were measured at 2-week intervals. Serum total protein, albumin, urea nitrogen, and creatinine were determined at week 8. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured at weeks 4 and 8. Renal injury was evaluated histopathologically. TCV and CAP reduced SBP at week 2 and proteinuria at week 8. GFR and RBF fell in all groups, but decreases were not significant in treated SHR and histopathological changes were significantly ameliorated. All blockade by TCV or CAP reduces renal injury in salt-loaded SHR with partial renal ablation. AII is essential in remnant kidney models of renal injury, and AII blockade is essential in renal protection by ACEI.
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PMID:Nonpeptide angiotensin II type 1 receptor antagonist prevents nephrosclerosis in hypertensive rats. 788 4

Endothelium-derived nitric oxide (EDNO) and angiotensin II play a role in the regulation of vascular tone and sodium handling. The objective of this study was to determine the role played by angiotensin II in mediating the arterial pressure and renal response to increments in sodium intake during chronic EDNO inhibition. Six groups of Wistar rats were studied; they were fed either a normal sodium diet (groups I, II, and III) or a high sodium diet (groups IV, V and VI). Rats in groups II, III, V and VI were placed on oral L-N-nitroarginine-methyl ester (L-NAME) for 4 weeks. In groups III and VI, the angiotensin II receptor antagonist, TCV-116, was administered. A significant increase in blood pressure was observed in group V compared with group II at the end of the experimental period. TCV-116 attenuated the L-NAME-induced hypertension in both group III and group VI. Urinary protein excretion and the glomerular sclerotic injury score in group V were greater than in group II. TCV-116 attenuated the proteinuria and glomerular injury induced by chronic EDNO inhibition in the groups with normal (group III) and high sodium intake (group IV). Systemic hypertension and glomerular injury were enhanced by salt loading during EDNO inhibition, and the angiotensin II receptor antagonist, TCV-116, attenuated this salt-induced increase in blood pressure and renal injury, suggesting that EDNO may counteract the renal effects of angiotensin II.
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PMID:Enhancement of hypertension and renal injury by salt-loading during chronic nitric oxide inhibition. Effects of TCV-116, a novel angiotensin II receptor antagonist. 788 7

Using the model of adriamycin-induced nephrotic syndrome in rats, we studied the relationship between urine electrolyte excretion rates and proteinuria and determined the activity of Na(+)-K(+)-ATPase in the renal tissue of nephrotic rats. No relationship was found between the increased sodium reabsorption and proteinuria. But the impaired salt excretion was inversely related to the increase of Na(+)-K(+)-ATPase activity in the renal inner medulla. It is proposed that direct effect of adriamycin on renal tubule cells is the primary events, that the increased Na(+)-ATPase activity on basolateral membrane of renal tubule cells be an intrarenal factor which mediates the action of retention of salt by the kidney and that inner medullary collecting ducts might be one of the sites of the sodium retention in nephrotic rats.
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PMID:Na(+)-K(+)-ATPase activity: role in the impaired sodium excretion of experimental nephrosis in rats. 795 2

It has been reported that focal and segmental glomerulosclerosis (FSGS) with pronounced proteinuria rapidly develop in Dahl salt-sensitive hypertensive (DS) rats fed a high-salt diet. We found that even when they are fed a standard rat chow (0.3% NaCl), DS rats, especially males, exhibit marked proteinuria, hypoalbuminemia, and hypertriglyceridemia without marked hypertension at 32 to 38 weeks of age. The nephrosis was associated with spontaneously developed FSGS. We therefore investigated the mechanism of hypertriglyceridemia in nephrotic animals. Plasma triglyceride (TG) and apoprotein (apo) B levels were markedly increased in DS rats compared with Sprague-Dawley (SD) rats, and this was mainly attributable to an increase in the concentration of very-low-density lipoprotein (VLDL). The TG secretion rate estimated by the Triton WR1339 method was significantly greater in DS rats. VLDL-TGs isolated from both the DS and SD rats were endogenously radiolabeled with different isotopes, and a mixture of these was then injected into DS and SD recipients. The half-life of VLDL-TG was about three times longer in DS recipients, regardless of the source of VLDL. In SD recipients, VLDL from DS rats was cleared at a slower rate than VLDL from SD rats. The activity of lipoprotein lipase in postheparin plasma was substantially decreased in DS rats. Isoelectric focusing gel electrophoresis (IEF) showed that the ratio of apo E/C or apo C-II/C-III in VLDL was markedly decreased and the ratio of apo E or apo C to apo A1 in high-density lipoprotein (HDL) was slightly decreased in DS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of hypertriglyceridemia in Dahl salt-sensitive rats, an animal model of spontaneous nephrotic syndrome. 812 10

The effects of long-term oral administration of the angiotensin-converting enzyme (ACE) inhibitor trandolapril (0.01 mg/kg [T0.01] and 1 mg/kg [T1]) on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats during the treatment period (5-20 weeks of age) and up to 8 weeks thereafter. During the treatment period T1, but not T0.01, limited the increase in blood pressure. However, both doses of trandolapril prevented stroke and mortality and strongly opposed (T0.01) or abolished (T1) the increases in saline intake, diuresis, and proteinuria observed in control animals. Simultaneously, trandolapril markedly prevented (T0.01) or abolished (T1) vascular fibrinoid necrosis formation in the brain, kidney, and heart. Finally, trandolapril dose-dependently reduced arterial thickening and glomerular and tubulointerstitial lesions in the kidney, as well as arterial thickening, infarction, and fibrosis in the myocardium. At 8 weeks after treatment withdrawal, the antihypertensive effect of T1 had disappeared, but stroke-related mortality and fibrinoid necrosis remained completely suppressed. Further, no additional cerebral, renal, or cardiac lesions developed, and no increase in proteinuria occurred. In the T0.01 group, 17% of the animals died, fibrinoid necrosis tended to develop, organ lesions worsened, and proteinuria strongly increased. We conclude that (1) early ACE inhibition with trandolapril affords a long-lasting protection versus stroke and mortality both during and after the treatment period; and (2) that this beneficial effect is due to the suppression of fibrinoid necrosis formation and not to the drug's antihypertensive action. In contrast, both properties appear to contribute to trandolapril's renal and cardiac protective effects.
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PMID:Trandolapril's protective effects in stroke-prone spontaneously hypertensive rats persist long after treatment withdrawal. 816 51


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