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 studied the effect of dietary supplementation with L-arginine for 6 weeks on the progression of renal disease in female Sprague-Dawley rats subjected to sham-operation (groups 1 and 2) or surgical ablation of 85% to 90% of the total renal mass (groups 3 and 4). All rats were fed a standard rat chow containing 22.8% protein. Rats in groups 1 (n = 5) and 3 (n = 9) served as controls and drank tap water ad libitum. Rats in groups 2 (n = 6) and 4 (n = 6) drank tap water supplemented with 1% L-arginine. Rats in groups 1 and 2 had similar values for glomerular and tubular function and serum chemistries 6 weeks after sham-operation. Sham-operated rats given L-arginine had significantly greater urine urea excretion than similar rats drinking tap water. Rats with subtotal nephrectomy (groups 3 and 4) had a significantly higher blood pressure, greater proteinuria, and a significantly lower plasma albumin than sham-operated rats (groups 1 and 2). Rats with remnant kidneys given 1% L-arginine (group 4) had significantly greater values for glomerular filtration rate (GFR) and P-amino hippurate (PAH) clearance than similar rats given tap water (group 3), despite comparable levels of systemic blood pressure, hematocrit, body weight, plasma chemistries, including L-arginine, and urine chemistries, except urea excretion. The remnant kidney of rats given L-arginine (group 4) had a greater number of normal or minimally abnormal glomeruli and fewer interstitial changes than that of rats given tap water (group 3).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary supplementation with L-arginine ameliorates the progression of renal disease in rats with subtotal nephrectomy. 846 29

Angiotensin converting enzyme (ACE) inhibitors, particularly enalapril and captopril, have been shown to decrease proteinuria in diabetic animals and human subjects. Since heparan sulfate proteoglycan confers a negative charge on the glomerular basement membrane, and either decreased synthesis or loss of this charge causes albuminuria in diabetic animals, we examined the possibility that enalapril prevents albuminuria through glomerular preservation of heparan sulfate in long-term diabetic rats. A total of 22 male Wistar rats were used in the study. Diabetes was induced in 15 rats by a single intraperitoneal injection of streptozotocin (60 mg/kg). The remaining 7 rats received buffer. One week following induction of diabetes, 8 diabetic rats were allowed to drink tap water containing enalapril at a concentration of 50 mg/liter; the remaining 7 diabetic and 7 nondiabetic rats were given only tap water. The drug treatment was continued for 20 weeks. Systolic blood pressure and 24-hr urinary excretion of albumin were measured at 2, 8, 16, and 20 weeks. At the end of 20 weeks, all rats were killed, kidneys were removed, and glomeruli were isolated by differential sieving technique. Total glycosaminoglycan and heparan sulfate synthesis was determined by incubating glomeruli in the presence of [35S]sulfate. Characterization of heparan sulfate was performed by ion-exchange chromatography. Systolic blood pressures were significantly lower in enalapril-treated diabetic rats compared to untreated diabetic rats. Diabetic glomeruli synthesized less heparan sulfate than glomeruli from nondiabetic rats. Also, glomerular heparan sulfate content of diabetics was significantly lower than that of nondiabetics. Further characterization of heparan sulfate showed that the fraction eluted with 1 M NaCl was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. Enalapril treatment normalized not only glomerular synthesis and content but also various fractions of heparan sulfate in diabetic rats. Diabetic rats excreted increased quantities of heparan sulfate and albumin than nondiabetic rats. Enalapril therapy prevented both these increases in diabetic rats. These data suggest that enalapril treatment improves albuminuria through preservation of glomerular heparan sulfate and prevention of its urinary loss in diabetic rats.
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PMID:Enalapril improves albuminuria by preventing glomerular loss of heparan sulfate in diabetic rats. 201 5

A 21 week experiment was conducted with male SPF Ico/Shoe: WIST rats to study the influence on diagnostic parameters of toxicological studies of (i) acidification of drinking water by hydrochloric acid (untreated tap water vs. pH 3 vs. pH 2), (ii) individual vs. group caging (5 animals/cage), and (iii) ad libitum vs. 10 ml restrictive water supply. Acidification to pH 2 resulted in a slightly but significantly reduced excretion of phenol red, lowered proteinuria and a decreased urine volume, whereas all other parameters remained unchanged. Individual caging was less stressful than expected from published data. Red blood cell counts were increased, water consumption and urine volume were somewhat lowered, but stress-sensitive parameters like adrenal weight, leucocyte and lymphocyte counts were not altered. A 10 ml restrictive water supply decreased urine volume, food consumption, body weight development and organ weights. Furthermore transient increases in red blood cell counts and hemoglobin contents, leucopenia and--most important--an impaired renal function were observed. In conclusion acidification of drinking water with hydrochloric acid should not be lower than pH 3, male Ico/Shoe: WIST rats can be regarded as minimum susceptible to individual caging, and reduced water intake might give false positive nephrotoxic effects.
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PMID:Effects of drinking water acidification, restriction of water supply and individual caging on parameters of toxicological studies in rats. 252 65

Serial determinations of protein excretion rate and systolic blood pressure (SBP) were made in spontaneously hypertensive rats (SHR) uninephrectomized (UNX) at six weeks of age and given tap water (CON), or water with hydrochlorthiazide, hydralazine and reserpine (HHR), captopril (CAP) or enalapril (ENP). Compared to CON, significant hypertension was prevented, kidney weight was lower and there was less proteinuria in HHR, CAP and ENP rats followed for 30 weeks after UNX. Morphologic studies of these four groups revealed that antihypertensive therapy reduced the incidence of glomerular sclerosis in UNX SHR by 50%. Despite complete absence of systemic hypertension, there was striking medial thickening of lobular arteries and arterioles of rats given the angiotensin converting enzyme (ACE) inhibitor, captopril. These vascular abnormalities were present to a lesser degree in rats given ENP, but were entirely absent in untreated animals or in those ingesting the HHR combination. Micropuncture studies performed five weeks after UNX in four additional groups of CON, HHR, CAP and ENP rats revealed that glomerular capillary pressure was elevated in CON and reduced by all three drug regimens. These studies support the hypothesis that glomerular capillary hypertension and/or nephron hypertrophy predispose to glomerular injury in this model of hypertension and reduced renal mass. ACE inhibitors and HHR are equivalent in their ability to prevent glomerular hypertension and damage in these rats, but the former, and in particular captopril, produce abnormalities of cortical vessels via a mechanism not dependent on the presence of systemic hypertension.
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PMID:Renal vascular effects of antihypertensive therapy in uninephrectomized SHR. 254 Mar 76

Taurine, a sulfur aminoacid, has been studied for a role in blood pressure regulation since it functions as a generalized inhibitory neurotransmitter and is found in high concentrations in the myocardium. We reinvestigated the magnitude of the hypotensive effect of chronic taurine administration to the spontaneously hypertensive rat (SHR) and the role of catecholamines in such an action. The SHR received either a 1% taurine solution or tap water to drink for 16 weeks. Taurine treatment caused a significant persistent reduction in blood pressure by 4 weeks that was maximal at 16 weeks (146 +/- 6 [exp.] v 182 +/- 5 [control] mm Hg, P less than .01). While this taurine-induced decline in blood pressure in the SHR was not accompanied by alterations in plasma epinephrine levels, there was a steady 235% increment in the norepinephrine concentration from 231 +/- 31 pg/mL initially to 542 +/- 126 pg/mL at completion of the study, P less than .02. The reduction in blood pressure was associated with decreased proteinuria in the taurine-treated SHR (9.6 +/- 4 [exp.] v 21.5 +/- 7 [control] mg/24 h, P less than .02) and less cardiac and renal hypertrophy. We conclude that taurine administration results in a 20 to 25% reduction in blood pressure in the SHR. The mechanism of this hypotensive action requires further study but is independent of changes in plasma catecholamine levels. The vasodepressor effect of taurine leads to less hypertensive injury to the kidney and heart in the SHR.
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PMID:Taurine lowers blood pressure in the spontaneously hypertensive rat by a catecholamine independent mechanism. 261 Sep 95

A case of primary myelofibrosis complicated with pericardial effusion and proteinuria is described. A 66-year-old female was admitted to our hospital because of abdominal fullness and shortness of breath. On admission, hepatosplenomegaly and pericardial effusion were observed. Blood examination revealed leukoerythroblastic anemia and thrombocytosis with tear drop cells and giant platelets. Bone marrow aspiration was dry tap and its biopsy showed remarkable myelofibrosis. Urinalysis indicated severe proteinuria. Although neutrophilic alkaline phosphatase score was low, no signs of acute blastic crisis of chronic myelogenous leukemia was found. The diagnosis of an atypical type of primary myelofibrosis was obtained. Administration of MCNU was started in August 1987. Hepatosplenomegaly, pericardial effusion and proteinuria were gradually improved after the administration. The etiology of the pericardial effusion and proteinuria were not obvious, however, these facts suggest that these abnormal findings might be related to PMF itself and MCNU was effective to PNF.
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PMID:[The use of MCNU to a patient of primary myelofibrosis complicated with pericardial effusion and proteinuria]. 276 70

Uninephrectomized male Munich-Wistar rats received either weekly subcutaneous injections of vehicle and water for drinking; injections of desoxycorticosterone (DOC) and 1% saline (SALT) for drinking; or DOC and SALT with hydrochlorthiazide, hydralazine, reserpine and KCl added. All studies were performed six weeks after UNX. At that time, rats receiving DOC and SALT alone were hypertensive and had significantly more proteinuria and morphologic evidence of glomerular injury than rats given vehicle and tap water which were normotensive. Antihypertensive therapy normalized mean arterial pressure in DOC-SALT rats, but failed to prevent proteinuria, mesangial expansion or focal segmental glomerular lesions. Micropuncture studies revealed that glomerular capillary pressure was elevated in both untreated and treated DOC-SALT animals. We conclude that drugs which successfully reduce systemic blood pressure may fail to correct glomerular capillary hypertension in DOC-SALT rats. As persistence of intrarenal hypertension is associated with significant glomerular injury, normalization of glomerular capillary pressure rather than systemic arterial pressure is crucial to the prevention of glomerular injury in this model.
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PMID:Glomerular hypertension and injury in desoxycorticosterone-salt rats on antihypertensive therapy. 357 36

Micropuncture and/or morphologic studies were performed in seven groups of uninephrectomized (UNX) adult male Munich-Wistar rats. Control groups 1, 3, and 6 received standard (24% protein) chow and tap water. Groups 2, 4, and 5 received weekly injections of desoxycorticosterone pivilate (DOC) and 1% saline for drinking, groups 2 and 4 were fed standard chow, and Group 5 a diet containing 6% protein. Group 7 received DOC, salt, and standard chow for 3 wk followed by withdrawal of DOC and salt for an additional 6 wk. 10-14 d after UNX, groups 1 and 2 exhibited similar single nephron glomerular filtration rates (SNGFR) and initial glomerular plasma flow rates (QA). Group 2 had higher mean arterial pressure (AP) and glomerular capillary hydraulic pressure (PGC) than group 1. 3-4 wk after UNX, group 4 exhibited further elevations in AP and PGC as compared with groups 2 and 3. SNGFR and QA were similar in groups 3 and 4, but these average values were greater than typical for normal rats. Group 4 also demonstrated increased urinary protein excretion. Morphologic evaluation of glomeruli in groups 2 and 4 revealed mesangial expansion and focal intraglomerular hemorrhage whereas glomeruli of groups 1 and 3 were essentially normal. Values for AP and PGC in group 5 were not different than group 3 but significantly lower than group 4. QA and SNGFR were lower in group 5 (low protein) than in groups 3 and 4. Furthermore, proteinuria and glomerular structural lesions were abolished in group 5. Morphologic studies performed in groups 6 and 7 showed that early DOC-SALT lesions progress to focal glomerular sclerosis. These studies suggest that continued elevations in glomerular capillary flows and pressures predispose to glomerular injury in this model of systemic arterial hypertension.
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PMID:Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. 671 46

Manipulations of metabolic acid-base status were used in an attempt to modify the renal handling and toxicity of the anticancer drug cisplatinum. Rats were orally pretreated with either tap water (TW), ammonium chloride (AC), or sodium bicarbonate (SB) for 3 days prior to intraperitoneal administration of a high cisplatinum dose (7.5 mg/kg b.w.). Urine was collected daily for 4 days between drug dosing and killing of the animals. AC-pretreated rats did not exhibit the characteristic cisplatinum-induced diuresis and were unable to maintain an acid urinary pH following drug administration. AC rats had a significantly lower, and SB rats a significantly higher, urinary excretion of platinum than did TW rats. Platinum excretion was found to be correlated with urinary pH (r = 0.88) and not urinary volume (r = 0.30). The renal concentration of platinum was greater in AC animals than in SB or TW animals, but no significant difference was observed in liver or plasma concentrations between the groups. Both pretreated groups had equal percent of free vs bound platinum. Proteinuria was more severe in AC-pretreated rats, but histologic evidence of renal tubular damage was present in all the three groups. It is concluded that metabolic acidosis can seriously impair the renal handling of high dose cisplatinum but that metabolic alkalosis offers no evident advantages over nonpretreatment.
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PMID:Changes in renal handling of platinum in cisplatinum-treated rats following induction of metabolic acidosis or alkalosis. 720 66

Endogenous nitric oxide plays an important role in modulation of renal hemodynamics and sodium handling, with increased nitric oxide production inducing renal vasodilation and natriuresis. In the normal rat, nitric oxide activity increases as an adaptive response to increased dietary salt intake, perhaps facilitating natriuresis and thus blood pressure homeostasis. We hypothesized that impaired nitric oxide synthetic ability would result in sensitivity to the pressor effects of high dietary salt intake. Four groups of normal Sprague-Dawley rats were observed for eight weeks: Control, 0.4% NaCl chow and tap water; Salt, 4% NaCl chow and tap water; NAME, 0.4% NaCl chow and water containing the nitric oxide synthase inhibitor, L-nitro-arginine-methylester; Salt+NAME, 4% NaCl chow and water containing L-nitro-arginine-methylester. Compared to Controls, Salt rats demonstrated a significant increase in urinary excretion rate of the stable nitric oxide metabolites, NO2 and NO3, and had no increase in blood pressure. Furthermore, Salt rats had no functional or structural evidence of renal injury. In contrast, Salt+NAME rats demonstrated a significantly higher blood pressure than NAME rats, and urinary NO2 and NO3 excretion rate did not increase despite high salt intake. After eight weeks, Salt+NAME rats had significantly impaired renal function and proteinuria. We conclude that adaptive changes in endogenous NO production play a critical role in sodium and blood pressure homeostasis. Furthermore, impaired nitric oxide synthase activity may be a pathogenetic factor in the development of salt-sensitive hypertension.
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PMID:Endogenous nitric oxide synthesis determines sensitivity to the pressor effect of salt. 752 54


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