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 compared the effects of the angiotensin-converting enzyme inhibitor enalapril and a conventional antihypertensive regimen (hydralazine and metoprolol) on kidney function, albuminuria, and glomerular ultrastructure in hypertensive diabetic and nondiabetic rats. Diabetes was induced with streptozocin at 8 wk of age in spontaneously hypertensive (SHR) rats. Antihypertensive drugs were administered in drinking water from the time of induction of diabetes in all groups. Blood pressure reduction was equal in the diabetic and nondiabetic SHR rats receiving either enalapril or hydralazine plus metoprolol. In diabetic SHR rats, there was a rise in serum creatinine after 32 wk, which did not occur in diabetic rats treated with either antihypertensive regimen or in nondiabetic rats. Both drug regimens reduced albuminuria in diabetic and nondiabetic SHR rats to a similar degree. Enalapril and the combination of hydralazine and metoprolol were associated with decreased glomerular basement membrane thickness and glomerular volume in diabetic and nondiabetic SHR rats without significant effect on fractional mesangial volume. Thus, antihypertensive therapy retards the development of albuminuria, glomerular basement membrane thickening, and glomerular hypertrophy in the rat in the presence or absence of diabetes. No specific benefit of angiotensin-converting enzyme inhibition was observed in these hypertensive models of nephropathy. Human studies comparing the effects of different classes of antihypertensive drugs on kidney function, proteinuria, and glomerular morphology are warranted.
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PMID:Nephropathy in model combining genetic hypertension with experimental diabetes. Enalapril versus hydralazine and metoprolol therapy. 224 81

Chronic aminonucleoside nephrosis is variably associated with tubulointerstitial damage, depending on the route and frequency of drug administration. Recently, different groups have shown this injurious tubulointerstitial process to be reversible, coinciding with the resolution of heavy proteinuria to normal values. The authors have previously shown that a single jugular intravenous administration of puromycin aminonucleoside (PA) to male Munich-Wistar rats produces a triphasic pattern of glomerular injury and proteinuria, which culminates in focal glomerulosclerosis 70 weeks after drug administration. The authors now report the later progression of the tubulointerstitial morphologic abnormalities associated with acute nephrosis (phase I), despite spontaneous resolution of glomerular injury during the intermediate period (phase II) in this model. Although treatment of rats with the angiotensin I converting enzyme inhibitor enalapril (50 mg/l drinking water) over the 70-week period did not affect the magnitude of proteinuria during the acute nephrotic phase, enalapril prevented the recurrence of proteinuria (phase III), as well as significantly reducing the severity of interstitial fibrosis, extent of tubular dilatation, and number of intratubular casts on semiquantitative scoring at the conclusion of the study. In addition, enalapril-treated rats had less low-molecular-weight protein excretion during the recurrent phase of proteinuria, suggesting a preservation of tubular functional capacity to reabsorb these proteins. In vitro cytotoxicity studies showed only the glomerular visceral epithelial cell to be sensitive to PA, in contrast with rat tubular epithelium and other cellular controls. Although the exact pathogenetic mechanism responsible for the development of the tubulointerstitial damage remains unknown, PA in vitro does not adversely affect rat tubular epithelium; there is however a clear correlation between the magnitude of recurrent proteinuria and the severity of tubulointerstitial morphologic abnormalities, as suggested by the beneficial effect of converting enzyme inhibition on both of these untoward processes.
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PMID:Irreversible tubulointerstitial damage associated with chronic aminonucleoside nephrosis. Amelioration by angiotensin I converting enzyme inhibition. 226 Jun 22

To label specific anionic sites on glomerular capillary wall structures, biotin was covalently linked to sialic acid residues by sequential treatment with mild peroxidation and biotin hydrazide, while carboxyl groups were biotinylated by exposure to the combination of biotin hydrazide and a water-soluble carbodiimide reagent. Optimal specific labeling of rat glomerular structures was obtained with in situ perfusion of the biotinylation reagents, followed by fixation in 4% phosphate-buffered paraformaldehyde, embedment in LR White resin, and post-embedment detection of biotinylated sites using a sequence of anti-biotin antibodies followed by a secondary antibody-colloidal gold conjugate. Attempts to use streptavidin-gold conjugates were not successful. Specificity of labeling was confirmed by enzymatic (neuraminidase) pre-treatment or by modification of carboxyl groups, as evaluated by electron microscopy and by solid-phase assays of solubilized glomerular basement membrane (GBM) components. In two rats with heavy proteinuria induced by doxorubicin (Adriamycin), a marked reduction in sialic acid residues within the GBM and on the epithelial cell surfaces was found, suggesting that reduced charge density attributable to abnormal sialylation may be important in the pathogenesis of nephrotic proteinuria.
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PMID:Affinity cytochemical labeling of glomerular basement membrane anionic sites using specific biotinylation and colloidal gold probes. 230 3

Metabolic acidosis is a common finding in uremia. The metabolic consequences, however, are poorly understood. Thus, the aim of our study was to assess the effect of chronic metabolic acidosis in 5/6-nephrectomized male Sprague-Dawley rats given a normal (18%; n = 19) and a low-protein diet (8%; n = 23). Each of these groups was sequentially given CaCO3 and CaCl2 in the drinking water for a fortnight each. The animals were randomly assigned to start either with CaCO3 or CaCl2 (random cross-over design). The blood pH decreased significantly in both CaCl2 groups (18% protein: CaCO3 7.18 vs. CaCl2 7.11; 8% protein: CaCO3 7.26 vs. CaCl2 7.09) as did standardized base excess (18% protein: CaCO3-5.9 vs. CaCl2-9.7; 8% protein: CaCO3-3.6 vs. CaCl2-12.6). Food intake declined during acidosis in both groups, but more in the 18% protein group. The same occurred with body weight (g) in the 18% group, which decreased dramatically (8% protein: CaCO3 389 vs. CaCl2 390; 18% protein: CaCO3 413 vs. CaCl2 366). The change in body weight was reflected in the urinary urea excretion (mg/24 h/g food) (8% protein: CaCO3 0.9 vs. CaCl2 1.0; 18% protein: CaCO3 2.2 vs. CaCl2 30.8). There was a significant increase in proteinuria (mg/24 h) in the 8% group (CaCO3 10 vs. CaCl2 15), while in the 18% group no real change occurred (CaCO3 24 vs. CaCl2 18). Factoring the proteinuria for food intake, however, also resulted in a tendency towards an increased proteinuria in the 18% group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A low-protein diet protects uremic rats against the negative sequelae of metabolic acidosis. 232 98

This study was undertaken to investigate the role played by renal functional and structural changes in the development of radiation-induced hypertension. Four groups of rats were studied: 1) left kidney radiated, 2) sham procedure, 3) uninephrectomy followed 3 weeks later by radiation of the contralateral kidney, and 4) uninephrectomy followed by sham procedure 3 weeks later. All radiated rats became hypertensive at 12 weeks (p less than 0.05) and had higher protein excretion (p less than 0.05). In the presence of an intact contralateral kidney, radiation causes mild-to-moderate histological abnormalities, and therefore, creatinine clearance and water and sodium handling do not change. Plasma renin activity increased in this group (p less than 0.05). Radiated uninephrectomized rats showed decreased creatinine clearance (p less than 0.05), but renin activity remained unchanged. These rats developed severe histological abnormalities in glomeruli, interstitia, tubuli, and vessels resulting in increased sodium and water output. The average of individual tubular and interstitial scores correlated significantly with both water intake and output but not with sodium excretion. These studies suggest that in the presence of an intact kidney, renin is an important determinant in the development or maintenance of radiation hypertension, whereas in the absence of the contralateral kidney, severe histological changes and renal failure are prominent despite increased water intake and output. The more severe glomerular sclerosis and proteinuria in the latter model could be related to diminished renal mass.
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PMID:Mechanisms of hypertension in renal radiation. 240 56

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

Comparative effects of the angiotensin converting enzyme inhibitors captopril and enalapril on progression of chronic renal disease was studied in 3/4 nephrectomized rats. Rats were divided into sham and nephrectomized groups, and treated with plain water or water containing captopril (150 mg/liter) or enalapril (50 mg/liter). Evaluations were made 4 weeks before and 0, 4, 8, and 10 weeks after nephrectomy. Endogenous creatinine clearance decreased in drug-treated, nephrectomized rats to values less than sham controls, but remained greater than water-treated rats. Significant (P less than 0.05) proteinuria developed 4 weeks post-nephrectomy in water-treated rats, 8 weeks post-nephrectomy in captopril-treated rats, but did not develop in enalapril treated rats. Regression analysis of carbamylated plasma protein values vs plasma creatinine revealed significant (P less than 0.05) relationships only in the water-treated, nephrectomized rats from weeks 0 through 8, but were otherwise unaffected by treatment. Both drugs resulted in significantly (P less than 0.05) improved scores for renal histologic lesions as compared to water treatment. Modifications of proteinuria in captopril and enalapril-treated rats occurred prior to onset of changes in systolic blood pressure, which was significantly elevated only in water-treated, nephrectomized rats at weeks 8 and 10. We conclude that angiotensin converting enzyme inhibitors may ameliorate progression of experimental renal disease through intrarenal effects, independent of modulation of systemic blood pressure, and that enalapril may be superior to captopril in some regards.
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PMID:Comparative effects of captopril and enalapril on the progression of chronic renal disease in partially nephrectomized rats. 255 51

The effect of long-term treatment with either enalapril or high dose verapamil on survival, proteinuria, blood pressure and renal morphology was studied in female Wistar rats with markedly reduced renal mass. Four weeks were allowed for remnant kidney hypertrophy before determining the response to renal ablation of individual animals regarding proteinuria and hypertension. At this time, five groups of 18 rats were formed with equal levels of proteinuria and hypertension. Groups E1 and E2 were treated with enalapril, groups V1 and V2 with verapamil, and one group served as control. The daily food allowance was 14 g/rat of a standard rat diet, containing 30% protein and 100 mmol NaCl/kg food in groups E1 and V1. NaCl content was reduced to 20 mmol/kg food in groups E2, V2 and control. The drugs were added to the drinking water, enalapril at a dose of 0.1 g/liter, verapamil at 0.5 to 0.7 g/liter. Drug intake thus amounted to 10 to 25 mg/kg for enalapril and 50 to 140 mg/kg for verapamil. Treatment was continued for 15 weeks. Three of the 18 control rats did not survive up to 15 weeks. Mortality was lower in the enalapril treated groups with a single nonsurvivor in group E1. In contrast, mortality was higher in the verapamil treated animals with seven nonsurvivors in group V1 and eight in group V2. Blood pressure control was excellent in both enalapril treated groups. and proteinuria decreased in most animals of group E1 and all of group 22. Glomerulosclerosis did not develop in the majority of the enalapril treated animals. Despite the high dose, verapamil barely lowered blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term enalapril and verapamil in rats with reduced renal mass. 255 83

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


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