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)

To test the effect of converting enzyme inhibition (CEI) on diabetes, with or without renal insufficiency, we studied streptozotocin-induced diabetic rats, with or without reduced renal mass, which were treated with insulin in sufficient amounts to maintain glucose values in the mild to moderately hyperglycemic range. We found that diabetes increased glomerular filtration rate (GFR) (inulin clearance, 2.3 +/- 0.5 ml/min vs 1.9 +/- 0.1 ml/min; p < 0.05) and blood pressure (137 +/- 15 mm Hg vs 116 +/- 6 mm Hg; p < 0.05) but did not increase plasma atrial natriuretic peptide (ANP) values, when compared with control rats (72 +/- 38 vs 68 +/- 24 pg/ml). CEI decreased GFR and blood pressure to control values. In rats with diabetes and concomitantly reduced renal mass, hypertension, elevated ANP values, proteinuria, and glomerulosclerosis were prominent features. CEI was associated with reduced blood pressure (172 +/- 17 mm Hg vs 138 +/- 15 mm Hg; p < 0.05), without a concomitant decrease in GFR (1.1 +/- 0.1 ml/min vs 1.1 +/- 0.1 ml/min). Further, CEI reduced the elevated ANP values (140 +/- 34 pg/ml vs 66 +/- 19 pg/ml; p < 0.05) to those of control rats. CEI reduced proteinuria by 50% and ameliorated the histopathologic changes. In separate experiments, rats with 5/6th nephrectomy and hypertension but without diabetes were also found to have elevated ANP levels that decreased to control values with CEI. The data speak for a renal protective effect of angiotensin I-converting enzyme inhibition in this model but do not support a specific role for ANP in the model of diabetes with concomitantly reduced renal mass.
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PMID:Effects of angiotensin-converting enzyme inhibition in diabetic rats with reduced renal function. 145 98

Male weanling Wistar rats received 200 micrograms/ml of mercury (Hg), as HgCl2, in drinking water for 180 days. At the end of the treatment, systemic arterial blood pressure was augmented, cardiac inotropism was reduced, and heart rate was unchanged. Light and electron microscopical studies of the kidney showed a mesangial proliferative glomerulonephritis in about 80% of the glomeruli. Tubular cells showed reduction of the acid phosphatase activity, which was related to functional abnormalities of the lysosomes. In the 24 hour urine samples of the Hg exposed rats, there was slight reduction of kallikrein activity, but evident proteinuria was not present in all samples. Plasma renin activity was reduced, that of angiotensin I-converting enzyme was augmented, and plasma aldosterone concentrations were unchanged. Mercury was accumulated mostly in the kidney of the Hg treated animals; and the content of Hg in the heart was higher than in the brain. These data show that chronic exposure to Hg acts on the kidney with complex mechanisms of toxicity; these contribute to modify systemic haemodynamics.
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PMID:Renal mechanisms in the cardiovascular effects of chronic exposure to inorganic mercury in rats. 157 Dec 92

The relationship between tubulointerstitial nephritis and proteinuria was characterized in experimental nephrosis in rats. In one group, proteinuria induced by aminonucleoside of puromycin (PAN) was reduced by using an 8% protein diet and adding the angiotensin I-converting enzyme (ACE) inhibitor enalapril to the drinking water. Two control groups were injected with saline and PAN, respectively, and fed a 27% protein diet. The first group had significantly reduced albuminuria and a definite attenuation of tubular cell injury. There was a strong positive correlation between the number of interstitial macrophages and albuminuria. The beneficial effect was reproduced by dietary-protein restriction alone, whereas ACE inhibition alone had an insignificant effect on the degree of proteinuria. Depletion of circulating T lymphocytes in one group of nephrotic rats eliminated interstitial lymphocytes but did not affect interstitial macrophage influx. Inhibition of the in situ proliferation of resident interstitial macrophages by unilateral kidney irradiation failed to change the intensity of the macrophage infiltration. Treatment of rats with sodium maleate produced proximal tubular cell toxicity but interstitial inflammation did not develop, suggesting that the latter is not a nonspecific response to tubular injury. These studies demonstrate a strong relationship between tubulointerstitial nephritis and the severity of proteinuria in experimental nephrosis.
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PMID:A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. 202 4

Puromycin aminonucleoside (PAN)-nephrotic rats have high serum angiotensin I-converting enzyme (ACE) activity. We studied ACE activity in serum, urine, and tissues from PAN-nephrotic rats on days 2, 6, 11, and 16 after PAN injection. Proteinuria and hypoproteinemia were evident on days 6 and 11. Though significantly decreased, proteinuria was still evident on day 16. Serum ACE activity increased on days 2, 6, and 11. Urinary ACE activity became evident on days 6, 11, and 16 and correlated positively with proteinuria, suggesting that the source of urine ACE is the blood serum. ACE activity increased in testis on days 2 and 6, in lungs and aorta on days 6 and 11, in adrenal glands and small intestine on day 11, and in kidney on days 11 and 16. Heart ACE activity decreased on days 2 and 6, and increased on day 16; brain ACE activity decreased on day 6 and increased on day 11. These data implicate that changes in tissue ACE content may contribute to elevate serum ACE in PAN-nephrotic rats.
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PMID:Angiotensin I-converting enzyme activity in puromycin aminonucleoside-nephrotic syndrome. 217 83

Proteinuria and progressive glomerulosclerosis are commonly associated with nephron loss. We studied the pathogenesis of these lesions by examining the role of changes in specific glomerular capillary wall permeability properties in uninephrectomized rats. The development of altered capillary permselectivity to macromolecules and loss of glomerular basement membrane anionic charge were measured by the dextran fractional clearance and ferritin tracer probe methods, respectively. In addition, the protective effect of dietary protein restriction and an angiotensin I-converting enzyme inhibitor (captopril) were studied in eight groups of male Sprague-Dawley rats. Four groups of rats underwent sham-nephrectomy or left nephrectomy and were fed an 8.5% protein diet (sham-nephrectomy and low protein, nephrectomy and low protein) or a 30% protein diet, respectively (sham-nephrectomy and high protein, nephrectomy a high protein). Four other groups of rats underwent sham-nephrectomy or left nephrectomy and were treated with captopril (50 mg/kg/day) while receiving a 8.5% protein diet (sham-nephrectomy, low protein and captopril, nephrectomy, low protein and captopril) or a 30% protein diet, respectively (sham-nephrectomy, high protein and captopril, nephrectomy, high protein and captopril). Rats were nephrectomized at 21 days of age and were functionally tested and sacrificed at 7 months of age. The nephrectomy and high protein rats had significantly greater proteinuria and higher fractional clearance of neutral dextrans in the 30 to 42 A range compared with that of sham-nephrectomy and high protein, nephrectomy and low protein, and nephrectomy, high protein and captopril rats. The nephrectomy and high protein rats also had a significantly lower labeling of the glomerular basement membrane with cationic ferritin tracer molecules compared with the nephrectomy and low protein and nephrectomy, high protein and captopril rats. Of the eight treatment groups, the nephrectomy and high protein rats had the most severe glomerular lesions. In general, nephrectomized rats fed low dietary protein and nephrectomized rats treated with captopril had significantly less proteinuria, glomerular lesions, and milder changes in the glomerular capillary wall porosity and glomerular basement membrane anionic charge.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of dietary protein and captopril on glomerular permselectivity in rats with unilateral nephrectomy. 245

The effect of varying doses of captopril, an angiotensin I-converting enzyme inhibitor, on renal hemodynamics, systemic arterial pressure, and the progression of chronic renal disease in conscious, three-quarter nephrectomized adult male Sprague-Dawley rats was studied. Six weeks following nephrectomy (Week 0), rats were randomly divided into five groups. Group 2 (n = 8), 3 (n = 8), 4 (n = 9), and 5 (n = 5) were given 5, 10, 20, and 40 mg/kg captopril, respectively, daily in drinking water. Group 1 (n = 7) and sham-operated controls (n = 7) were given water only. On Weeks -6, 0, 2, and 4, renal function was assessed by 24-hr urinary protein excretion and plasma creatinine. Systolic blood pressure was measured at these times by the tail cuff method. Following Week 4, glomerular filtration rate and effective renal plasma flow were measured in conscious rats by single injection clearance of [3H]inulin and [14C]tetraethylammonium bromide, respectively. Group 1 had significantly higher (P less than 0.05) 24-h urinary protein excretion, plasma creatinine, and systolic pressure compared with Group 5 and controls by Week 4, whereas values for these parameters for Groups 2-4 ranged between these extremes. Although systolic pressures were not significantly different (P greater than 0.05), Group 2 had significantly lower proteinuria than Group 1 (P less than 0.05) at Week 4. Total kidney glomerular filtration rate was similarly decreased in Groups 1-5 compared with control rats. Total kidney effective renal plasma flow was higher in captopril-treated groups than in Group 1, whereas systolic blood pressure was similar or lower, indicating that captopril reduced renal vascular resistance. Furthermore, unlike Groups 1-3, the groups receiving higher doses of captopril (4 and 5) did not develop anemia associated with chronic renal disease. In conclusion, captopril attenuated renal functional deterioration in a dose-related manner. The effect on proteinuria was evident at low doses of captopril which did not significantly reduce systemic blood pressure and was accompanied by an increase in effective renal plasma flow and a decrease in renal vascular resistance.
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PMID:Dose effect of captopril on renal hemodynamics and proteinuria in conscious, partially nephrectomized rats. 264 43

Micropuncture and morphologic studies were performed in six groups of male Munich-Wistar rats after removal of the right kidney and segmental infarction of two-thirds of the left kidney. Groups 1 and 4 received no specific therapy. Groups 2 and 5 were treated with the angiotensin I-converting enzyme inhibitor, enalapril, 50 mg/liter, in the drinking water. Groups 3 and 6 were treated with reserpine (5 mg/liter), hydralazine (80 mg/liter), and hydrochlorothiazide (25 mg/liter). All rats were fed standard chow. Groups 1-3 underwent micropuncture study 4 wk after renal ablation. Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR) due to high average values for the mean glomerular transcapillary hydraulic pressure gradient (delta P) and glomerular plasma flow rate (QA). In group 2 rats, treatment with enalapril prevented systemic hypertension and maintained delta P at near-normal levels without significant reduction in SNGFR and QA. In contrast, triple drug therapy normalized systemic hypertension, but failed to lower delta P in group 3 rats. Groups 4-6 were followed for 12 wk after renal ablation. Untreated group 4 rats demonstrated continuous systemic hypertension, progressive proteinuria, and glomerular structural lesions, including mesangial expansion and frequent areas of segmental sclerosis. In group 5 rats, treatment with enalapril maintained systemic blood pressure at normal levels over the 12-wk period and dramatically limited the development of proteinuria and glomerular lesions. Despite equivalent systemic blood pressure control in group 6 rats, failure of triple drug therapy to control glomerular hypertension was associated with progressive proteinuria and glomerular lesions comparable to those seen in untreated group 4 rats. Thus, unless glomerular capillary hypertension is corrected, control of systemic blood pressure is insufficient to prevent progressive renal injury in rats with reduced renal mass.
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PMID:Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. 301 63

Micropuncture and morphological studies were performed in three protocols assessing the renal hemodynamic and structural effects of angiotensin I-converting enzyme inhibitors (CEIs) in the progression of glomerular injury. In protocol I, rats were subjected to 5/6 renal ablation and received no therapy, enalapril (CEI), or triple-drug therapy (TRX) for 12 weeks. Control of systemic and glomerular hypertension with CEI resulted in prevention of glomerular capillary hypertension and protection against glomerular injury. Despite equivalent control of systemic BP, failure of TRX to control glomerular hypertension was associated with no protection against eventual proteinuria and glomerular sclerosis, values for these indexes being as abnormal as in rats receiving no therapy. In protocol II, rats were again subjected to 5/6 renal ablation and followed for 18 weeks. Early institution of CEI soon after ablation again prevented systemic and glomerular hypertension and largely limited glomerular injury. In a third group, enalapril therapy was delayed for 8 weeks after ablation until hypertension and proteinuria were established. Late institution of CEI resulted in prompt reduction in systemic and glomerular capillary hypertension and stabilization of glomerular disease. In protocol III, CEI was administered to normotensive, moderately hyperglycemic diabetic rats. A modest, 20-mm Hg reduction in systemic arterial pressure was associated with the normalization of glomerular capillary pressure and a striking reduction in the development of albuminuria and glomerular injury. These studies suggest that CEI effectively prevent glomerular capillary hypertension and thereby afford protection against glomerular injury in diverse models of progressive renal disease.
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PMID:Therapeutic implications of converting-enzyme inhibitors in renal disease. 303 94

In search of genetic determinants of susceptibility to diabetic nephropathy, we examined the association between DNA sequence differences at the locus of angiotensin I-converting enzyme (ACE) and renal complications in 151 insulin-dependent diabetes mellitus (IDDM) patients with a diabetes duration of 16-21 years. This nested case-control study included 77 normoalbuminuric control subjects (albumin excretion rate < 30 micrograms/min) and 74 cases with evidence of nephropathy ranging from microalbuminuria to overt proteinuria. DNA from each of these patients was genotyped at the ACE locus by a three-allele restriction fragment-melting polymorphism (RFMP) (Dde I), which we described recently, and a two-allele insertion/deletion recognized as an Xba I restriction fragment-length polymorphism, which has been shown by other investigators to be associated with serum levels of ACE and with risk of myocardial infarction. The least common allele of the Dde I RFMP was significantly more frequent among cases with nephropathy than among normoalbuminuric control subjects (12.8 vs. 4.5%, P < 0.05). The deletion in the ACE gene was also more frequent in case than in control subjects (56.1 vs. 47.4%), but the difference was not statistically significant (P < 0.25) with this sample size. To determine the independence of these associations, the two polymorphisms were analyzed jointly to identify Xba I/Dde I haplotypes. As might be expected, carriers of the Xba I/Dde I '+ =' haplotype had a fourfold risk of developing diabetic nephropathy (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.5-11.0). However, this did not explain all of the excess Xba I '+' allele among cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetic predisposition to diabetic nephropathy. Evidence for a role of the angiotensin I--converting enzyme gene. 790 24

The effect of angiotensin I-converting enzyme inhibition (ACEI) on the age-related changes in the kidney structure and function was investigated in rodents. Normotensive male Wistar (WAG)/Rij rats were treated with perindopril from the age of 6 mo to the day of killing at 12, 24, or 30 mo. Mean blood pressure, constant from 6 to 30 mo, was reduced by 19 mmHg in treated animals. With age, the major functional modifications were a decrease in glomerular filtration rate and in renal blood flow, a rise in intrarenal vascular resistance (IVR), a reduced tubular reabsorption of salts, and a progressive increase in proteinuria. ACEI significantly reduced IVR and proteinuria. From a structural point of view, the glomeruli showed 1) an increase in size, 2) a decrease in capillary surface, 3) a diffuse thickening of the glomerular basement membrane, 4) an expansion of the mesangial matrix, and 5) an accumulation of albumin droplets in podocytes inducing 6) a dispersed focal and segmental glomerulosclerosis which, at 30 mo, affected < 2% of glomeruli. Of these six age-related structural changes, ACEI delayed the appearance of the three latter changes.
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PMID:Effect of chronic ANG I-converting enzyme inhibition on aging processes. I. Kidney structure and function. 816 Aug 53


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