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)

Tonic basal release of nitric oxide (NO) by vascular endothelial cells controls blood pressure (BP) in the basal state. In these studies we investigated the effects of chronic inhibition of basal NO synthesis in the rat for a 2-mo period. Significant systemic hypertension developed in chronically NO-blocked rats compared to controls. Marked renal vasoconstriction was also observed with elevations in glomerular blood pressure (PGC) and reductions in the glomerular capillary ultrafiltration coefficient (Kf). Chronically NO-blocked rats also develop proteinuria and glomerular sclerotic injury compared to controls. These studies therefore describe a new model of systemic hypertension with glomerular capillary hypertension and renal disease due to chronic blockade of endogenous NO synthesis. These observations highlight the importance of the endogenous NO system in control of normal vascular tone and suggest that hypertensive states may result from relative NO deficiency.
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PMID:Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage. 163 15

Spontaneously hypertensive rats (SHR) that underwent uninephrectomy (UNX) at six weeks of age were randomly assigned to receive no treatment, the calcium channel blocker, nifedipine, or the angiotensin converting enzyme inhibitor, enalapril. Both drugs reduced systemic blood pressure, however, blood pressure tended to be greater in rats given nifedipine than in those on enalapril. After six months, proteinuria and the relevance of glomerula sclerosis were significantly reduced in the two treated groups compared to values observed in untreated SHR. Kidney weight was also reduced by therapy, suggesting that both enalapril and nifedipine inhibited compensatory kidney growth. Micropuncture studies performed in similarly treated groups of rats, but at 11 weeks of age, revealed that PGC was elevated in untreated UNX SHR and reduced by both nifedipine and enalapril. These findings support the hypothesis that glomerular hypertension and renal hypertrophy are important risk factors for glomerular injury. They suggest that calcium blockers are as effective as angiotensin converting enzyme inhibitors in preventing progressive kidney damage.
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PMID:Effects of nifedipine and enalapril on glomerular structure and function in uninephrectomized SHR. 189 65

A number of studies based on animal models of both diabetes and renal insufficiency have shown that adequately reducing blood pressure attenuates the progression of glomerulosclerosis and decreases urinary protein excretion. Furthermore, compared with conventional antihypertensive therapy, angiotensin converting enzyme (ACE) inhibitors show a greater benefit in reducing these parameters. Nineteen published animal studies have investigated the effects of calcium antagonists on renal hemodynamics and glomerulosclerosis, but only three of them have evaluated the use of calcium antagonists with models of diabetes. Of six micropuncture studies based on a 1 5/6 nephrectomy model of renal insufficiency, five demonstrated reduced efferent arteriolar resistance, two showed reduced glomerular capillary pressure (PGC), and two showed significantly reduced proteinuria and glomerulosclerosis. Studies using nifedipine with both the unilaterally nephrectomized DOCA salt rat model and the 1 5/6 nephrectomy model demonstrated reduced proteinuria and glomerulosclerosis that was independent of reduced PGC. Two separate micropuncture studies of the spontaneously hypertensive rat model also found reduced efferent arteriolar resistance and PGC as well as proteinuria. Finally, studies of Dahl "salt-sensitive" rats showed an early decrease in glomerulosclerosis without a significant change in either proteinuria or glomerulosclerosis after five weeks. The results of eleven clinical studies of diabetic patients have been published; they showed divergent effects of calcium antagonists on renal function and urinary protein excretion. In the various animal models, the divergent renal hemodynamic and histologic effects reported for calcium antagonists may be largely due to the equality of blood pressure reduction, the varied baseline hemodynamic profiles, and the divergent status of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal effects of calcium antagonists in diabetes mellitus. An overview of studies in animal models and in humans. 191 Jun 42

Serial measurements were performed in Munich-Wistar rats with five-sixths nephrectomy that had undergone prior selective thyroidectomy (Tx group) or thyroidectomy with thyroxine replacement (TxT4 group) to determine the effects of Tx on glomerular and tubular dynamics in relation to Tx attenuation of renal failure progression. At 1 week, inulin clearance rates (Cin) in TxT4 and Tx rats were 0.367 +/- 0.171 and 0.120 +/- 0.036 mL/min, respectively, different at P less than 0.01. Corresponding single-nephron filtration rate (SNGFR), glomerular plasma flow (QA), glomerular transcapillary hydraulic pressure (delta P), and proximal tubular reabsorption (Jv) were all reduced in Tx compared with TxT4 rats (P less than 0.01). Protein excretion (UPROT) was 151 +/- 40 in TxT4 rats, and 9 +/- 5 mg/d in Tx animals. Glomerular mesangial matrix expansion and focal tubulointerstitial changes were more frequent in TxT4 than Tx rats. By 4 weeks, Cin, SNGFR, QA, glomerular ultrafiltration coefficient (Kf) and Jv were similar in Tx and TxT4. Only glomerular capillary pressure (PGC) remained lower in Tx rats (35 +/- 3 v 50 +/- 3 mm Hg in TxT4, P less than 0.001). UPROT was 161 +/- 24 in TxT4 and 17 +/- 12 mg/d in Tx rats. While 7% +/- 4% of glomeruli showed focal sclerosis in TxT4 rats, there was none in the Tx group. Maximal glomerular planar area increased between 1 and 4 weeks in the TxT4 group, but not in the Tx group. However, this measurement was not significantly different between TxT4 and Tx glomeruli at 1 or 4 weeks. Minimal focal tubulointerstitial changes were found in TxT4, but there were not progressive from those observed at 1 week. The reduced PGC at 1 week was the result of a disproportionately greater increase in afferent (RA) than efferent arteriolar resistance (RE) in Tx rats (P less than 0.025); however, at 4 weeks, both RA and RE had decreased to values identical to those in TxT4 animals and the lower PGC in Tx rats was the result of a reduced mean arterial pressure. In conclusion, a reduced PGC was the sole functional correlate of decreased proteinuria and glomerulosclerosis afforded by Tx in this partial nephrectomy model. Suppression of either nephrectomy-related hypertrophy or tubulointerstitial injury by Tx could not be excluded as at least partially protective factors.
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PMID:Serial glomerular and tubular dynamics in thyroidectomized rats with remnant kidneys. 199 65

The purpose of this study was to examine the course of residual glomerular function in two models of renal ablation both with equivalent degrees of nephron reduction (1 1/3 nephrectomy). The remnant group underwent right nephrectomy and infarction of one third of the left kidney, yielding constant proportions of remnant deep and superficial nephrons, while the bromoethylamine (BEA) group underwent right nephrectomy and chemical ablation by BEA (50 mg intravenously [IV]) of the deep nephrons of the left kidney, leaving superficial nephrons. Ten weeks following ablation, greater whole kidney permselective defects indicative of worse injury occurred in the remnant group compared with the BEA group, as manifested by increased excretion of total protein (.65 +/- .14 v .23 +/- .04 g/d [65 +/- 14 v 23 +/- 4 mg/24 h]; P less than 0.05) and greater fractional clearance of albumin (71.8 +/- 42.1 v 9.0 +/- 3.4 X 10(-4); P less than 0.05) and IgG (17.9 +/- 10.2 v 3.6 +/- 1.2 x 10(-4); P less than 0.05). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were similar in the ablated groups, but lower than a sham-operated control group. Superficial single nephron GFR (SNGFR) and mean glomerular capillary pressure (PGC) were elevated similarly in the ablated groups compared with the control group. Based on the differences in the two models, the site of the increased proteinuria in the remnant group could be the deep nephrons and/or the nephrons adjacent to the scar.
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PMID:Comparison of residual glomerular function in experimental papillary necrosis and renal infarction. 238 47

Single nephron filtration rate of albumin (SNGFRAlb) was measured in remnant nephrons of Munich-Wistar rats 4-6 wk after subtotal nephrectomy (NPX). Serial thin-section histological analysis was then conducted on the same glomeruli by light microscopy. SNGFRAlb ranged from 1 to 15 times normal. However, a direct relationship between abnormalities of structure and function was not seen, e.g. the glomeruli with the fewest structural abnormalities and marked hyperfiltration often had the highest SNGFRAlb. Moreover, the majority of glomeruli had minimal structural abnormalities. Normalization of the markedly elevated glomerular capillary pressure (PGC) in these glomeruli was accomplished by acute intravenous infusion of verapamil, which decreased SNGFRAlb by 9-83% without affecting the single nephron filtration rate of water (SNGFRH2O). 1-2 wk after subtotal NPX, all glomeruli were hyperfiltering and had elevated PGC. The fractional clearance of larger (greater than 36 A) dextrans was selectively increased in these glomeruli that lacked discernible damage by light microscopy. Verapamil normalized PGC, reduced proteinuria to 48 +/- 4% of baseline, and improved glomerular size selectivity without altering SNGFRH2O. Proteinuria after subtotal NPX thus originates largely from glomeruli with minimal structural abnormalities. The defect in size selectivity is largely attributed to the prevailing high PGC, producing large, nonselective channels on the glomerular capillary wall. The observations raise the possibility that in chronic renal diseases, the reduction in proteinuria often seen after therapeutic measures, including antihypertensive medication, may reflect their functional effect on the relatively intact glomeruli rather than their structure-sparing effect on severely damaged glomeruli, which contribute little to the proteinuria.
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PMID:"Intact nephrons" as the primary origin of proteinuria in chronic renal disease. Study in the rat model of subtotal nephrectomy. 318 57

Munich-Wistar rats (MWF/Ztm), originally selected for high number of superficial glomeruli, were used to correlate abnormal urinary protein excretion with glomerular hemodynamics and glomerular morphology. Two animal groups were used, one of male and one of female rats. They were kept periodically in metabolic cages to determine urinary protein excretion. All animals were fed standard rat chow. In male animals protein excretion, evaluated at seven weeks of age, was already significantly higher than in females (17 +/- 11 vs. 8 +/- 3 mg/24 hr), and then progressively increased averaging 291 +/- 51 mg/24 hr at week 21. In females urinary protein excretion was within the normal range up to week 18 and averaged 25 +/- 13 mg/24 hr at week 21. Body and kidney weight at the end of the experimental period were significantly higher in males than in females. Whole kidney inulin clearance (CIn) and single nephron glomerular filtration rate (SNGFR) were significantly higher in male than in female rats, while mean glomerular capillary hydraulic pressure (PGC) and transcapillary hydraulic pressure difference (delta P) were comparable. Single nephron glomerular plasma flow (QA) and afferent and efferent arteriolar resistance were comparable in male and female rats. The calculated glomerular ultrafiltration coefficient (Kf) was significantly higher in male than in female MWF/Ztm rats. No significant differences were detected between the two groups in the total number of glomeruli, and in glomerular size. These findings indicate that male MWF/Ztm rats develop spontaneous proteinuria, which progressively increases with the age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sex related differences in glomerular ultrafiltration and proteinuria in Munich-Wistar rats. 319 67

Male Munich-Wistar rats were subjected to 1 2/3 nephrectomy. One group received no therapy (C). A second group received daily doses of methylprednisolone (MP). A third group received MP plus the angiotensin I converting enzyme inhibitor (CEI) benzazepril. A fourth group received CEI alone. Half of the rats in each group underwent micropuncture study 2 weeks after ablation. Untreated rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR), due to glomerular capillary hyperperfusion and hypertension. Administration of MP resulted in comparable systemic hypertension with further elevation of SNGFR due to even higher values for glomerular perfusion and hydraulic pressure (PGC). Concurrent treatment with CEI-controlled systemic and glomerular hypertension despite equivalent renal ablation and comparable doses of MP. After 12 weeks untreated rats demonstrated continued systemic hypertension, progressive proteinuria, and eventual glomerular sclerosis. Addition of MP dramatically accelerated the development of proteinuria and glomerular sclerosis, while CEI afforded striking protection against disease progression. Thus, potent vasodilator glucocorticoids may amplify hemodynamically mediated glomerular injury, whereas control of systemic and glomerular hypertension prevents this undesirable consequence of chronic steroid therapy.
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PMID:Glucocorticoids amplify glomerular injury in rats with renal ablation. 337 Jan 34

Male Munich-Wistar rats wer subjected to 1 2/3 nephrectomy. One group received no therapy. A second group received the angiotensin converting enzyme (ACE) inhibitor enalapril. A third group received triple therapy (TRX) with reserpine, hydralazine and hydrochlorothiazide. Half of the rats underwent micropuncture study 4 weeks after nephrectomy. Untreated rats exhibited high systemic blood pressure (SBP) and single-nephron hyperfiltration due to high values for the mean glomerular capillary hydraulic pressure (-PGC) and glomerular capillary plasma flow rate (QA). The ACE inhibitor therapy controlled both SBP and -PGC. In contrast, TRX normalized SBP but failed to lower -PGC. After 12 weeks untreated rats demonstrated systemic hypertension, progressive proteinuria and extensive glomerular sclerosis. The ACE inhibitor dramatically limited proteinuria and sclerosis. Despite equivalent SBP control with TRX, failure to control -PGC resulted in proteinuria and sclerosis comparable with the untreated rats. Thus unless -PGC is controlled, SBP control may be insufficient to prevent renal injury.
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PMID:Antihypertensive therapy must control glomerular hypertension to limit glomerular injury. 355 75

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


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