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)

We used streptozotocin (STZ) to induce the animal model of diabetes mellitus in rats. On the 7th and 14th days of induction, kidney disorder, the levels of NO3- in plasma and tissue homogenate in different periods were observed. The NO3- levels in relation to the application of L-arginine (L-Arg) were also noted. The results showed that the kidney weight/body weight ratio significantly increased in different periods (P < 0.05). On the 7th day profuse proteinuria appeared and it markedly increased on the 14th day: creatinine clearance rate (Ccr) significantly raised, too (P < 0.005). The NO3- levels in plasma and tissue homogenate were getting higher with time. The level of NO3- significantly increased after L-Arg was perfused. It indicated that kidney disorder was present at the early stage of diabetes, and the raised Ccr indirectly indicated the increase of glomerular filtration rate. These suggest that NO3- and L-Arg may be important mediums which have effects of hyperfiltration and hyperperfusion of glomerulus.
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PMID:[L-arginine and nitric oxide have effects on glomerulus hyperperfusion of early diabetic rats]. 1068 27

During gestation endothelium induces decreases in vascular responses to vasopressor agents but endothelium disease is followed by hypertension and enhanced vascular reactivity during preeclampsia. In a rat model of preeclampsia induced by NO synthase inhibition we study here isolated aortic contractions. From day 13 of gestation 2 groups of Wistar female rats were fed control (C) or nitro-arginine enriched diets (0.063%, i.e. 30 mg/kg/d) (treated) (T). On gestational day 20 systolic blood pressure (SBP, mmHg) is measured by tail cuff method and isolated thoracic ring aorta contractions are studied after depolarisation (KCl 60 mM) or norepinephrine (cumulative concentrations 10-9 M-10-5 M). After chronic NOS inhibition, hypertension develops: SBP is 154 +/- 2.17 in T and 116 +/- 3.75 in C, p < 0.01 and significant proteinuria (mg/d) appears: T, 63.4 +/- 21.6 versus C 3.08 +/- 0.48, p < 0.01. NO synthase inhibition in treated rats impairs the depressed contractile response obtained in the presence of endothelium in control rats but addition of L-arginine suppresses the effect of nitroarginine. Taking in account our results and those described in literature it appears that L-arginine treatment could ameliorate some pathologic pregnancies.
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PMID:[Nitric oxide and isolated aortic contraction in a pregnant hypertension model by the inhibition of nitric oxide synthase in pregnant Wistar rats]. 1079 54

Men are at greater risk for renal injury than women. We studied whether male rats are more sensitive to the hypertensive and proteinuric effects of chronic nitric oxide synthase (NOS) inhibition than female rats. In addition, we studied whether androgens or estrogens are responsible for differences in sensitivity to proteinuria induced by chronic NOS inhibition. Females and males were treated with 10, 20, 30, and 100 mg/l N(omega)-nitro-L-arginine (L-NNA) during 24 wk. Systolic blood pressure (SBP) and proteinuria were measured regularly and compared with time-control measurements in control females and males. In females and males treatment with 10 mg/l L-NNA had no effect on SBP or proteinuria. Treatment with 20, 30, and 100 mg/l L-NNA resulted in a dose-dependent increase in SBP that was similar in males and females. However, females treated with 20 and 30 mg/l L-NNA were resistant to the development of proteinuria: maximum values were 16 +/- 7 and 46 +/- 21, respectively, vs. 16 +/- 3 mg/day in controls, whereas males treated with those doses showed an increase in proteinuria [139 +/- 35 (P < 0.05) and 318 +/- 82 (P < 0.01), respectively, vs. 55 +/- 11 mg/day in controls]. Treatment with 100 mg/l L-NNA increased proteinuria similarly in both females and males. To study the role of sex hormones in differences in sensitivity to proteinuria induced by mild chronic NOS inhibition, treatment with 20 mg/l L-NNA was repeated in ovariectomized (Ovx) and orchidectomized rats. Ovariectomy did not affect the increase in SBP caused by 20 mg/l L-NNA, but, in contrast to intact females, this dose of L-NNA did cause Ovx rats to develop proteinuria (51 +/- 16 vs. 16 +/- 7 mg/day in control Ovx rats; P < 0.05). Orchidectomy completely prevented the increased SBP as well as proteinuria induced by 20 mg/l L-NNA in male rats. In conclusion, male rats are more sensitive than female rats to develop proteinuria induced by mild chronic NOS inhibition. Estrogens provide some protection in females, whereas androgens are responsible for the increased sensitivity of male rats to proteinuria induced by mild chronic NOS inhibition. Risk factors associated with a compromised nitric oxide system may be more detrimental to the kidney in men than in women.
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PMID:Male gender increases sensitivity to proteinuria induced by mild NOS inhibition in rats: role of sex hormones. 1099 16

To determine the role of aldosterone in mediating cardiovascular damage, we performed ablation/replacement experiments with aldosterone in a rat model of cardiac injury. Administration of angiotensin II and Nomega-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor) to male rats drinking 1% saline caused hypertension, severe biventricular myocardial necrosis, proteinuria, and fibrinoid necrosis of renal and cardiac vessels. Removal of aldosterone by adrenalectomy or through administration of the selective aldosterone antagonist eplerenone markedly reduced the cardiac and renal damage without significantly altering blood pressure. Aldosterone infusion in adrenalectomized, glucocorticoid-replaced L-NAME/angiotensin II-treated animals restored damage. Thus, we identified aldosterone as a critical mediator of L-NAME/angiotensin II induced vascular damage through mechanisms apparently independent of its effects on systolic blood pressure.
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PMID:Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. 1101 44

Increased apoptosis of glomerular cells, with progression of glomerulosclerosis, overactivity of the renin-angiotensin system and elevation of glomerular pressure, follows chronic nitric oxide synthase (NOS) inhibition in spontaneously hypertensive rats (SHR). To gain insight into the regulation of glomerular cell apoptosis in severe nephrosclerosis, we investigated apoptosis, the expression of proliferative cell nuclear antigen (PCNA) in glomeruli, and glomerular morphometric changes in 20-week-old SHR, SHR treated with NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 80 mg/l in drinking water), and SHR treated with L-NAME and the calcium antagonist, efonidipine (20 mg/kg per day), for 3 weeks. Apoptosis in non-sclerotic glomeruli was quantified by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. The increase in systolic blood pressure and the severe proteinuria with severe nephrosclerosis induced by chronic NOS inhibition were completely prevented by efonidipine. Furthermore, the glomerular area and capillary tuft area were markedly increased in rats treated with efonidipine compared with both control rats (+30 and +42%, respectively, p<0.01) and rats treated with L-NAME (+35 and +56%, respectively, p<0.01)-treated rats. This calcium antagonist also significantly inhibited the both increases of the glomerular cell apoptosis index (-72%) and the PCNA index (+44%), therefore the alteration between apoptosis and proliferation slightly increased the number of glomerular cells (subcapsular, +22%, p<0.01; juxtamedullary, +2%, not significant). Thus, the calcium antagonist efonidipine seems to play an important role in the regulation of apoptosis and proliferation of glomerular cells and may be effective in preventing nephrosclerosis exacerbated by NOS inhibition.
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PMID:Calcium antagonist inhibits glomerular cell apoptosis and injuries of L-NAME exacerbated nephrosclerosis in SHR. 1113 Dec 82

Chronic nitric oxide (NO) synthase (NOS) inhibition results in renal injury. Hypertension is an important risk factor for renal injury. We studied the influence of preexistent hypertension on the sensitivity for renal injury induced by chronic NOS inhibition in rats. Spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were treated with 3, 10, 30 and 100 mg/l Nomega-nitro-L-arginine (L-NNA) until death. Systolic blood pressure and proteinuria were measured regularly and compared with time-control measurements in untreated SHR and WKY. In WKY, 3 and 10 mg/l L-NNA did not affect systolic blood pressure, while 30 and 100 mg/l L-NNA resulted in an increase in systolic blood pressure after 12 and 4 weeks, respectively. In contrast in SHR, every dose of L-NNA resulted in an increase in systolic blood pressure after 2 weeks. In WKY, 3 and 10 mg/l L-NNA did not affect proteinuria or survival, while 30 and 100 mg/l L-NNA resulted in an increase in proteinuria after 30 and 9 weeks, and a median survival of 36 and 12 weeks, respectively. In SHR, 3, 10, 30 and 100 mg/l L-NNA resulted in an increase in proteinuria after 30, 12, 3 and 3 weeks, and a median survival of 41, 20, 5 and 3 weeks, respectively. Thus, at every dose of the inhibitor, chronic NOS inhibition resulted in far earlier increases in systolic blood pressure and proteinuria and a marked increase in mortality in SHR as compared to WKY. Indeed, a very low dosage of L-NNA that caused no harm in WKY was followed by marked increases in proteinuria and blood pressure and decreased survival in SHR. Hypertension strongly increases the vulnerability to cardiovascular risk factors that compromise the NO-system.
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PMID:Predisposition of spontaneously hypertensive rats to develop renal injury during nitric oxide synthase inhibition. 1113 73

To elucidate the role of nitric oxide (NO) and renin-angiotensin system (RAS) in the development of salt-sensitive hypertension, we investigated the pressor responses and renal histologic changes after long-term inhibition of endogenous NO synthesis in Dahl-Iwai salt-sensitive (DS) and salt-resistant (DR) rats under salt-re-stricted conditions that exaggerate RAS activation. Male DS and DR rats (6 weeks old) were fed with a low-salt (0.3%) diet for 5 weeks. NG-nitro-L-arginine (L-NA; dissolved in 60 mg/L deionized water), an arginine analogue acting as a NO-inhibitor, was also administered for 5 weeks. L-NA administration induced a gradual increase in systolic blood pressure (SBP) in both strains, and the pressor response in DS rats was apparently more enhanced relative to that in DR rats. Urinary nitrate plus nitrite (u-NOx) excretion was decreased by L-NA, with a significant negative correlation between SBP and u-NOx excretion in DS rats but not in DR rats. Plasma renin activity and urinary aldosterone level were significantly increased in L-NA-treated DS rats on week 5. Marked histologic changes with glomerular sclerosis and increased proteinuria and urinary N-acetyl-beta-glucosaminidase excretion were found in L-NA-treated DS rats but not DR rats. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that angiotensin II type 1 receptor (AT1R) mRNA level was significantly lower in DS rats than in DR rats at week 2, and that L-NA administration significantly reduced glomerular AT1R level of DS rats at week 5, possibly because of downregulation. Our results showed that, even under sodium restriction, the pressor response and renal injury induced by chronic NO inhibition were markedly more enhanced in DS rats than in DR rats, which indicates that depletion of NO participates in both the development of hypertension and glomerular injury in DS rats through a potential activation of RAS irrespective of sodium loading. These data suggest that endogenous NO is an essential determinant of salt-sensitive hypertension in DS rats.
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PMID:The role of nitric oxide and the renin-angiotensin system in salt-restricted Dahl rats. 1128 Dec 41

We previously demonstrated that a methionine-threonine-supplemented low (8.5%) casein diet (8.5CMT) reduced symptoms such as proteinuria in nephritic rats without severe protein malnutrition. In this study, we examined whether or not L-arginine supplementation to 8.5CMT would exacerbate proteinuria and other symptoms in nephritic rats. Male Wistar rats with glomerulonephritis induced by a single intravenous injection of nephrotoxic serum were fed either a 20% casein diet (control), 8.5% casein diet, 8.5CMT, or L-arginine-supplemented 8.5CMT (8.5CMTA) for 16 days. The 8.5CMTA, as compared with the 8.5CMT, aggravated proteinuria and glomerulonephritis. Administration of L-N(G)-nitroarginine methyl ester, an inhibitor of nitric oxide synthase, to 8.5CMTA-fed nephritic rats by drinking water for 14 days canceled the adverse effect of L-arginine on proteinuria and histopathological damage in glomeruli. These results suggest that the supplementation of L-arginine makes exacerbation via nitric oxide production in glomerulonephritis.
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PMID:Arginine as an exacerbating factor for glomerulonephritis in rats fed a methionine-threonine-supplemented low casein diet. 1144 Jan 31

Nitric oxide (NO) regulates inflammatory responses partly by cell-specific inhibition of the transcription factor nuclear factor kappaB (NF-kappaB). This study investigated the effect of continuous oral administration of an NO donor (molsidomine [Mol]), NO precursor (L-arginine [L-arg]), or selective inhibitors of inducible NO synthase (iNOS; aminoguanidine [AG], L-N(6)-(1-iminoethyl)lysine [L-NIL]) on the progression of tubulointerstitial inflammation and NF-kappaB activation in a non-immune model of chronic glomerular disease (Adriamycin nephropathy [AN]), from day 8 until day 30 after disease induction. On day 30, rats with AN had heavy proteinuria, reduced creatinine clearance, and tubulointerstitial disease. Treatment with both AG and L-NIL exacerbated the progression of AN as evidenced by (1) increased renal cortical malondialdehyde; (2) reduced creatinine clearance; and (3) increased tubular atrophy, interstitial volume, and monocyte infiltration. Unexpectedly, Mol also increased renal malondialdehyde and worsened tubular injury, whereas L-arg had no effect. The increase in renal cortical NF-kappaB activation in AN was not altered by AG, L-NIL, or Mol, but the mRNA expression of monocyte chemoattractant protein-1, interleukin-10, and osteopontin were elevated in these groups. Nitrite release from kidney slices reduced in AN. Treatment with Mol restored renal nitrite release to normal, whereas neither L-arg nor the NOS inhibitors had an effect. It is concluded that endogenous iNOS-derived NO has a protective role against tubulointerstitial injury and cytokine production in AN. However, the pro-oxidant activity of NO donors may limit their potential benefit in proteinuric renal disease.
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PMID:Pharmacologic modulators of nitric oxide exacerbate tubulointerstitial inflammation in proteinuric rats. 1146 42

Anew model of thrombotic microangiopathy (TMA) was previously developed, and it was demonstrated that endothelial nitric oxide (NO) synthase (NOS) is upregulated in glomeruli in this model. It was hypothesized that the synthesis of NO, a potent vasodilator and platelet inhibitory factor, is induced as a defense mechanism. The goal of this study was to clarify the role of NO in this model. Ex vivo experiments using Western blotting and functional assays demonstrated upregulation of endothelial NOS in isolated glomeruli from TMA rats. In in vivo experiments, five groups of rats were studied, including rats with TMA treated with vehicle, N(G)-nitro-L-arginine methyl ester (L-NAME) (a NOS inhibitor), or L-N(6)-(1-iminoethyl)lysine (L-NIL) (a specific inducible NOS inhibitor) and normal control rats treated with vehicle or L-NAME. Blood urea nitrogen levels, BP, urinary nitrate/nitrite excretion, and proteinuria were measured. Histologic assessments using periodic acid-Schiff staining and immunohistologic studies with markers for endothelium, platelets, fibrin, cell proliferation, and apoptosis were also performed. L-NAME inhibition of NO synthesis in rats with TMA resulted in more severe glomerular and tubulointerstitial injury, which was accompanied by thrombus formation and a marked loss of endothelial cells, with more apoptotic cells. These changes were associated with severe renal function deterioration. In contrast, these features were less pronounced in the vehicle- or L-NIL-treated rats with TMA and were absent in the control animals. In conclusion, inhibition of NO production in this model of TMA markedly exacerbated renal injury. The absence of effects with L-NIL treatment suggests a minor role for inducible NOS in this model. These results suggest that production of NO, most likely by endothelial cells, is an important protective mechanism in TMA.
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PMID:Protective role of nitric oxide in a model of thrombotic microangiopathy in rats. 1156 7


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