scholarly journals Angiotensin II modulates glomerular capillary permselectivity in rat isolated perfused kidney.

1996 ◽  
Vol 7 (5) ◽  
pp. 653-660 ◽  
Author(s):  
R Lapinski ◽  
N Perico ◽  
A Remuzzi ◽  
F Sangalli ◽  
A Benigni ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Excretion Rate ◽  
Rat Kidney ◽  
Renin Angiotensin System ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Converting Enzyme Inhibitors ◽  
Glomerular Capillary ◽  
Protein Excretion ◽  
Fractional Clearance

Studies in experimental animals and humans have documented that inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors reduces urinary protein excretion rate and retards the development of renal injury. Here we sought to investigate whether angiotensin II (All) modified the size-selective properties to macromolecules of the glomerular capillary barrier in isolated perfused rat kidney preparation. Compared with basal values, continuous All infusion into the renal artery at the rate of 3 or 8 ng/min, but not at 0.6 ng/min, induced a progressive and significant increase in urinary protein excretion rate. Evaluation of the sieving properties of the glomerular barrier by fractional clearance of polydisperse Ficoll showed that All significantly enhanced the filtration of tracer molecules of radil > or = 34A. All-induced changes in urinary protein excretion rate and in Ficoll fractional clearance were completely prevented by pretreatment with the specific All Type 1 receptor antagonist SR 47436.

scholarly journals The effect of high-dose angiotensin II receptor blockade beyond maximal recommended doses in reducing urinary protein excretion

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S196-S198 ◽  
Author(s):  
Marc S Weinberg ◽  
Adam J Weinberg ◽  
Raymond Cord ◽  
Dion H Zappe
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitors ◽  
Candesartan Cilexetil ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
High Dose ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Protein Excretion

The optimal doses of angiotensin-converting enzyme inhibitors (ACE-I) and/or angiotensin II receptor blockers (ARBs) for maximal reduction in urinary protein excretion are not known. Moreover, beneficial effects from ARBs, such as tissue protection owing to a more complete blockade of the renin-angiotensin-aldosterone system (RAAS), may be independent of blood pressure-lowering by ARBs. In this investigation, we evaluated whether increasing the dose of candesartan cilexetil, in subjects already on the maximally-recommended FDA doses of 32 mg, would induce a further reduction in 24-hour urinary protein excretion in patients with heavy proteinuria (urinary protein excretion >1.5 g/day; mean 4.4±2 g/day). Ten patients were started on 16 or 32 mg of candesartan cilexetil daily. After 1—2 months of therapy, the dose was titrated upwards to 96 mg. In all subjects, there were further reductions in 24-hour urinary protein excretion when the dose was increased beyond the recommended 32 mg maximal dose. Increasing the dose of candesartan cilexetil to 96 mg was safe, as most subjects showed no changes in serum potassium and, as expected, only a slight increase (0.5—0.7 mg/dl) in serum creatinine. These data warrant further investigation, since some subjects may require higher doses of candesartan to achieve optimal regression of proteinuria.

scholarly journals Platelet-activating factor mediates angiotensin II-induced proteinuria in isolated perfused rat kidney.

1997 ◽  
Vol 8 (9) ◽  
pp. 1391-1398
Author(s):  
N Perico ◽  
R Lapinski ◽  
K Konopka ◽  
S Aiello ◽  
M Noris ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Rat Kidney ◽  
Platelet Activating Factor ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Isolated Kidney ◽  
Protein Excretion ◽  
Paf Receptor ◽  
Paf Receptor Antagonist

Isolated kidney preparations (IPK) from male Sprague Dawley rats perfused at constant pressure were used to evaluate the effect of angiotensin II (AII) and platelet-activating factor (PAF) on renal function and urinary protein excretion. Compared with basal, intrarenal infusion of AII at 8 ng/min caused a progressive increase in protein excretion (11 +/- 6 versus 73 +/- 21 micrograms/min) in parallel with a decline in renal perfusate flow (RPF) (29 +/- 3 versus 18 +/- 3 ml/min). Addition to the perfusate of PAF at 50 nM final concentration also induced proteinuria (9 +/- 4 versus 55 +/- 14 micrograms/min) but did not change RPF (29 +/- 3 versus 30 +/- 3 ml/min). Preexposure of isolated kidneys to the PAF receptor antagonist WEB 2086 prevented the increase in urinary protein excretion induced by AII infusion (basal: 13 +/- 6; post-AII: 12 +/- 7 micrograms/min) but failed to prevent the vasoactive effect of AII (RPF, basal: 30 +/- 2; post-AII: 21 +/- 3 ml/min). In additional experiments, dexamethasone reduced the proteinuric effect of PAF remarkably. These results indicate that in isolated kidney preparation: (1) AII infusion induced proteinuria and decreased RPF; and (2) the effect of AII in enhancing urinary protein excretion was completely prevented by a specific PAF receptor antagonist, which, however, did not influence the AII-induced fall in RPF. It is suggested that PAF plays a major role in AII-induced changes in the permselective function of the glomerular capillary barrier.

Abstract P031: Reduced Augmentation Of The Intrarenal Renin-angiotensin System (ras), Lower Systolic Blood Pressure, And Preserved Renal Function In Female Compared To Male Rats With Unilateral Renal Artery Stenosis

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Annie L Bell ◽  
Weijian A Shao ◽  
Akemi Katsurada ◽  
Ryosuke Sato ◽  
L Gabriel G NAVAR
Keyword(s):  
Renal Function ◽  
Renal Artery ◽  
Renal Artery Stenosis ◽  
Renin Angiotensin System ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Artery Stenosis ◽  
Female Rats ◽  
Male Rats ◽  
Protein Excretion

Despite growing evidence of sex differences in the progression of hypertension, there are no guidelines that differentiate treatment between men and women. Intrarenal renin-angiotensin system (RAS) activation and tissue injury in 2-kidney, 1-clip (2K1C) hypertensive rats have been characterized in previous studies of male but not female rats. To evaluate possible sex differences in response to renovascular hypertension, urinary angiotensinogen (uAGT) excretion, systolic blood pressure (BP), urinary protein excretion, and renal function were assessed in female rats.Female (n=8) and male (n=6) rats underwent placement of a 0.2 mm clip on the left renal artery to simulate unilateral renal artery stenosis. BP was measured by tail-cuff plethysmography, and clearance studies were conducted in anesthetized rats to assess renal function. Urine protein concentration was determined by pyrogallol red method. uAGT was measured by ELISA as an index of intrarenal RAS activity. Systolic BP increased from 120±1 to 176±8 mmHg, and urinary protein excretion reached 20.2±5.6 mg/day in female rats. Although uAGT excretion increased from 13.2±7.7 ng/day to 74.1±29.9 ng/day in female rats, male rats had a significantly higher uAGT excretion of 1572.6±750 ng/day. Nonclipped kidneys exhibited more uAGT excretion compared to clipped kidneys, consistent with previous findings in males. Although 2K1C female rats demonstrate significantly lower renal function than sham females, they show more preserved renal function than male rats. Female rats also demonstrate significantly lower increases in systolic BP and urinary protein excretion compared to male rats. The data support substantial sex-dependent differences in renal responses to unilateral renal artery stenosis. The results show substantial increases in systolic BP, uAGT, and urinary protein excretion and decreased renal function after renal artery clipping in females, but the magnitude of the changes is markedly lower than in males. Nonclipped kidneys of both sexes exhibit greater uAGT excretion than clipped kidneys. Notably, females show less augmentation of the intrarenal RAS compared to male rats in renovascular hypertension.

Glomerular size selectivity in nephrotic rats exposed to diets with different protein content

1987 ◽  
Vol 253 (2) ◽  
pp. F318-F327
Author(s):  
A. Remuzzi ◽  
C. Battaglia ◽  
L. Rossi ◽  
C. Zoja ◽  
G. Remuzzi
Keyword(s):  
High Protein Diet ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
High Protein ◽  
Protein Diet ◽  
Standard Diet ◽  
Size Selectivity ◽  
Protein Excretion ◽  
Fractional Clearance ◽  
Glomerular Size

Glomerular size-selective properties in animals made nephrotic by adriamycin (ADR) injection and fed standard (20% protein) or high-protein (35% protein) diets were investigated using dextran fractional clearances. To interpret filtration and dextran-sieving data, a theoretical approach previously developed for analysis of experimental data in healthy and nephrotic humans was used. Four types of hypothetical pore-radius distributions were compared in order to establish the best tool for describing membrane pore structure in normal and nephrotic rats. This analysis revealed that a spread distribution of pores, the lognormal probability distribution, is the most adequate in representing membrane intrinsic characteristics. ADR animals on standard diet developed massive proteinuria and a lower glomerular filtration rate (GFR) than control animals. High-protein feeding in ADR rats induced a further increase in urinary protein excretion and in GFR. Dextran fractional clearance was more elevated for larger dextran fractions (greater than 46 A) in ADR animals on the standard diet than in control rats. No differences were observed in dextran-sieving curves between ADR rats on the standard and high-protein diet. Theoretical analysis of filtration and fractional clearance data revealed comparable changes in the intrinsic parameters of glomerular size selectivity in the two groups of nephrotic animals. These observations indicate that increased traffic of plasma proteins through the glomerular capillary wall does not imply, in our experimental condition, a further loss of glomerular size-selective properties. The greater urinary protein excretion of ADR animals on high-protein diet than ADR animals on a standard diet cannot be explained by further impairment of glomerular size selectivity but more likely reflects hemodynamic changes.

Antiproteinuric Effect of Angiotensinconverting Enzyme Inhibitors and an Angiotensin II Receptor Blocker in Patients with Lupus Nephritis

2009 ◽  
Vol 37 (3) ◽  
pp. 892-898 ◽  
Author(s):  
N Kitamura ◽  
Y Matsukawa ◽  
M Takei ◽  
S Sawada
Keyword(s):  
Renal Function ◽  
Angiotensin Ii ◽  
Lupus Nephritis ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Protein Excretion ◽  
Dsdna Antibody ◽  
Losartan Treatment

Although the effects of angiotensin II receptor blockers (ARBs) on non-diabetic glomerulonephritis have been reported, studies of their effects on collagenvascular diseases, particularly lupus nephritis, are limited. In this retrospective, observational study, systemic lupus erythematosus (SLE) patients ( n = 7) with lupus nephritis and uncontrolled proteinuria were treated with an angiotensin-converting enzyme inhibitor followed by the ARB losartan (25–50 mg/day). Urinary protein excretion and renal function were evaluated. After 12 months of losartan, mean urinary protein excretion decreased significantly by 84.8%. Mean systolic and diastolic blood pressures also decreased significantly during the 12 months of losartan treatment, although not in normotensive patients. Complement 4, total complement activity and anti-dsDNA antibody levels, which are indices of SLE activity, and serum creatinine levels, which is an index of renal function, showed no change in response to losartan treatment. A more extensive evaluation of the effects of ARBs in patients with lupus nephritis and poorly controlled proteinuria is required.

scholarly journals The nephropathy of non-insulin-dependent diabetes: predictors of outcome relative to diverse patterns of renal injury.

1998 ◽  
Vol 9 (12) ◽  
pp. 2336-2343 ◽  
Author(s):  
P Ruggenenti ◽  
V Gambara ◽  
A Perna ◽  
T Bertani ◽  
G Remuzzi
Keyword(s):  
Early Diagnosis ◽  
Serum Creatinine ◽  
Tissue Injury ◽  
Excretion Rate ◽  
Renal Tissue ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Protein Excretion ◽  
Insulin Dependent

Nephropathy of non-insulin-dependent diabetes mellitus (NIDDM) is the most common cause of end-stage renal failure (ESRF) in Western countries. This study investigates the clinical and histologic putative predictors of disease progression, with the final goal to identify patients at risk who may benefit from early diagnosis and intervention. It examines by repeated measurements of BP, blood glucose, serum creatinine, and urinary protein excretion rate 65 consecutive NIDDM patients with clinical, persistent proteinuria and biopsy-documented typical diabetic glomerulopathy (class I; n = 30), predominant nephroangiosclerosis (class II; n = 23), or nondiabetic type glomerulopathy (class III; n = 12), whose severity of renal tissue involvement was precisely quantified by a global histologic score. Baseline parameters and progression to renal end points, i.e., doubling of baseline serum creatinine, dialysis, or transplantation, were univariately and multivariately correlated by proportional hazards regression models. The median kidney survival time in the overall study population was 3.07 yr. Thirty-seven percent of patients reached an end point during a median (range) follow-up of 1.8 yr (0.4 to 5.7 yr). By univariate and multivariate analysis, kidney survival significantly correlated with baseline urinary protein excretion rate (P = 0.04 and P = 0.04, respectively) and renal tissue injury score (P = 0.0001 and P = 0.02, respectively), but not with the histologic classes. Patients with a urinary protein excretion rate < or = 2 g/24 h, or > 2 g/24 h with a histologic score < 7, never reached an end point. All patients with urinary protein excretion > 2 g/24 h and a histologic score > 13 progressed to ESRF over a median of 1.6 yr. No differences in other baseline parameters or in BP and diabetes control during follow-up accounted for these different outcomes. In NIDDM as well as in nondiabetic chronic renal disease, quantification of urinary protein excretion rate--independent of the pattern of underlying glomerular involvement--reliably discriminates progressors from nonprogressors and, combined with precise quantification of renal tissue injury, reliably predicts risk of ESRF. This information may be used to set guidelines for early diagnosis and appropriate intervention to reduce the number of diabetic patients who will need renal replacement therapy in years to come.

Differential evolution of blood pressure and renal lesions after RAS blockade in Lyon hypertensive rats

2002 ◽  
Vol 283 (5) ◽  
pp. R1041-R1045 ◽  
Author(s):  
Delphine Bertram ◽  
Nelly Blanc-Brunat ◽  
Jean Sassard ◽  
Ming Lo
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Histological Changes ◽  
Angiotensin System ◽  
Renal Lesions ◽  
Protein Excretion

The present work aimed to assess, in Lyon hypertensive (LH) rats, whether an early and prolonged inhibition of the renin-angiotensin system (RAS) could result in a blood pressure (BP) lowering and nephroprotection that persist after its withdrawal. Male LH rats received orally from 3 to 12 wk of age either an angiotensin-converting enzyme inhibitor perindopril at the doses of 0.4 and 3 mg · kg−1· day−1or an AT1receptor antagonist losartan at the dose of 10 mg · kg−1· day−1. BP, histological changes in the kidney, and urinary protein excretion were examined during and 10 wk after cessation of the treatments. Both perindopril and losartan decreased BP, prevented renal lesions, and limited urinary protein excretion. After cessation of the treatment, BP returned to the level of never-treated LH rats in rats having received 3 mg · kg−1· day−1of perindopril while it remained slightly lower in those treated with 0.4 mg · kg−1· day−1of perindopril or with losartan. This lack of marked persistent antihypertensive effect contrasted with a durable decrease in urinary protein excretion and improvement of the renal histological lesions. In conclusion, it is possible to separate the BP-lowering effects of RAS blockade from those on glomerulosclerosis and urinary protein excretion.

scholarly journals Increased cathepsin D-like activity in cortex, tubules, and glomeruli isolated from rats with experimental nephrotic syndrome

1984 ◽  
Vol 223 (2) ◽  
pp. 393-399 ◽  
Author(s):  
W H Baricos ◽  
S V Shah
Keyword(s):  
Nephrotic Syndrome ◽  
Cathepsin D ◽  
Rat Kidney ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Rat Tissues ◽  
Puromycin Aminonucleoside ◽  
Protein Excretion ◽  
Normal Rat ◽  
Functional Areas

We have examined the activity and distribution of cathepsin D (EC 3.4.23.5), a major renal lysosomal endoproteinase, in the various anatomical and functional areas of normal rat kidney. Cathepsin D-like activities (delta A280/h per mg of protein) in normal rat tissues were: cortex, 0.78 +/- 0.05, n = 37; medulla, 0.62 +/- 0.03, n = 12; papilla, 0.63 +/- 0.04, n = 12; tubules, 0.74 +/- 0.04, n = 28; glomeruli, 0.59 +/- 0.03, n = 28; and liver, 0.41 +/- 0.02, n = 28. Enzyme activity was maximal at pH 3.0-3.5 and inhibited more than 90% by pepstatin (6.7 micrograms/ml), suggesting that the enzyme is cathepsin D. In subsequent experiments we measured cathepsin D-like activity in cortex, tubules and glomeruli isolated from rats with puromycin aminonucleoside (PAN)-induced nephrotic syndrome. Treated animals (15 mg of PAN/100g body wt., intraperitoneally) developed proteinuria beginning 4 days after injection and exceeding 900 mg/24h on day 9. In two separate experiments involving 52 animals we observed a significant increase in cathepsin D-like activity in cortex (+82.7%), tubules (+109.6%) and glomeruli (+54.7%) isolated from PAN-treated rats killed during marked proteinuria (day 9, mean total urinary protein excretion: 937 +/- 94 mg/24h). This increase was observed whether the activity was expressed per mg of DNA or per mg of protein. Increased cathepsin D-like activity was first observed in cortex and tubules coincident with the onset of proteinurea (day 4, mean total urinary protein excretion: 112 +/- 23 mg/24h). In contrast with the significant elevation of renal cathepsin D-like activity, the activity (nmol/h per mg of protein) of alpha-L-fucosidase (EC 3.2.1.51), a non-proteolytic enzyme, was markedly decreased in the identical samples used for the measurement of cathepsin D-like activity: cortex (-46.4%); tubules (-46.1%); and glomeruli (-38.5%). In addition to changes in renal enzyme activities, PAN-treated rats excreted large amounts of cathepsin D-like activity in their urine (beginning on day 3) compared with nearly undetectable cathepsin D-like activity in the urine from control rats. The significant increases in glomerular and tubular cathepsin D activity may reflect an important role for this enzyme in the pathophysiology associated with PAN-induced nephrotic syndrome.

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