angiotensinogen and Nephrotic-Syndrome

Renin-angiotensin system (RAS) inhibitors reduce glomerular injury and proteinuria, indicating that angiotensin II (Ang II) is involved in glomerular diseases. Although the local RAS is reported to play an essential role in maintaining local tissue functions, the role of the local RAS in regulating glomerular function is not well evaluated. In this study, we analyzed the glomerular expression of RAS components in nephrotic models and the effect of Ang II receptor blockers (ARB) on the expression of angiotensinogen (AGT).. The levels of glomerular expression of RAS components were analyzed in two nephrotic models: anti-nephrin antibody-induced nephropathy and PAN nephropathy, a mimic of human minimal change nephrotic syndrome. The effect of the ARB irbesartan on the expression of AGT in the nephrotic model was analyzed.. Glomerular expression of AGT and the receptors for Ang II was clearly increased in the nephrotic models, while the expression levels of renin, ACE and ACE2 were decreased. ARB treatment suppressed the increase of glomerular expression of AGT in the nephrotic model.. It is conceivable that the promoted local RAS action participated in the glomerular dysfunction, and that ARB treatment ameliorated slit diaphragm injury by inhibiting the positive feedback loop of the activated local Ang II action.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensinogen; Animals; Cells, Cultured; Disease Models, Animal; Female; Kidney Glomerulus; Membrane Proteins; Nephrotic Syndrome; Podocytes; Rats, Wistar; Renin-Angiotensin System; RNA, Messenger

The clinical course of Henoch-Schönlein Purpura (HSP) in children is variable, with some patients having a much more rapidly progressing course than others. We investigated whether polymorphisms of the renin-angiotensin system (RAS) genes are involved in HSP. Three RAS genotypes were examined in 114 children with HSP and in 164 healthy children: the angiotensin I converting enzyme (ACE) insertion/deletion polymorphism, the M235T mutation in the angiotensinogen gene (Agt), and the A1166C in the angiotensin II type I receptor (AT1R) gene. Significant differences were observed between HSP patients and control group in the frequency of ACE and Agt genotypes (p=0.004 and p=0.003, respectively). The TT genotype of Agt gene was associated with a 3.5-fold increased risk for Henoch-Schönlein nephritis (HSN) compared with the MM/MT genotype (odds ratio, 3.5; 95% confidence interval, 1.2-10.4). There was a trend to a higher prevalence of the TT genotype of the Agt gene among patients with nephrotic range proteinuria when compared to the patients with mild proteinuria, although the difference did not reach a statistical significance. The results of this study suggest that polymorphisms of ACE gene and Agt gene likely influence the risk of developing HSP. However, among the three genes of the RAS studies, only Agt gene was associated with the susceptibility to HSN. RAS gene polymorphisms studied are not associated with the presence of nephrotic range proteinuria. Additional studies are warranted to verify the correlation between RAS gene polymorphisms and susceptibility to HSP.

Topics: Adolescent; Alanine; Angiotensinogen; Child; Child, Preschool; Cysteine; DNA Transposable Elements; Female; Gene Deletion; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; IgA Vasculitis; Kidney Diseases; Male; Methionine; Nephrotic Syndrome; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Proteinuria; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Severity of Illness Index; Threonine

Plasma angiotensinogen (Ao) concentration (PAC), urinary Ao excretion (UAE), hepatic levels of Ao mRNA and plasma renin concentration (PRC) were studied in control and nephrotic rats subjected to the following treatments: dexamethasone (DEX), ethinyl-estradiol (EE), tri-iodothyronine (T3), bilateral nephrectomy (NX), captopril (CAP) and adrenalectomy (ADX). In nephrotic rats PAC diminished, UAE and PRC augmented and Ao mRNA levels were not altered. In control rats, DEX, EE, T3 and NX increased PAC and Ao mRNA levels whereas CAP diminished PAC but not affected Ao mRNA. ADX diminished PAC and Ao mRNA levels. In nephrotic rats, these treatments produced the same effect than in control rats except in ADX which did not affect PAC. These data suggest that the decreased PAC is not related to alterations in hepatic Ao gene expression but to elevated PRC and UAE.

Topics: Adrenalectomy; Angiotensinogen; Animals; Captopril; Dexamethasone; Ethinyl Estradiol; Gene Expression Regulation; Liver; Male; Nephrectomy; Nephrotic Syndrome; Rats; Rats, Wistar; Renin; RNA, Messenger; Triiodothyronine

Plasma concentration and urine excretion of the renin-angiotensin system proteins are altered in rats with nephrotic syndrome (NS). In this work the messenger ribonucleic acid (mRNA) levels of angiotensinogen (Ao) were analyzed with the slot-blot hybridization technique in liver and other extrahepatic tissues: kidney, heart, brain, and adrenal gland from control, nephrotic, and pair-fed (PF) rats. NS was induced by a single injection of puromycin amino-nucleoside (PAN). Although a great urinary excretion and half-normal plasma levels of Ao were observed on day 6 after PAN injection, when NS was clearly established, hepatic Ao mRNA levels did not change. Furthermore, the Ao mRNA levels did not change in any of the extrahepatic tissues studied on day 6, nor did its hepatic levels at days 1, 3, 5, or 7 after PAN injection. These data suggest that the hepatic and extrahepatic Ao mRNA levels are unaltered during the development of the acute NS induced by PAN.

Topics: Acute Disease; Adrenal Glands; Angiotensinogen; Animals; Brain; Gene Expression; Kidney; Liver; Male; Myocardium; Nephrotic Syndrome; Nucleic Acid Hybridization; Puromycin Aminonucleoside; Rats; Rats, Wistar; RNA, Messenger; Tissue Distribution

Activity of the renin-angiotensin system in the nephrotic syndrome was investigated in rats with acute nephritis induced by anti-glomerular basement membrane (GBM) antibody. Injection of anti-GBM antibody resulted in a transient 2-fold elevation of both plasma renin and angiotensinogen with a peak at 12 h. Angiotensinogen mRNA levels in the liver also rapidly and transiently increased 4-fold at 3 h. The manifestation of acute nephritis, indicated by proteinuria, hypoalbuminemia, hypercholesterolemia and an increase in serum creatinine, following injection of anti-GBM antibody, was inhibited by a single administration of the selective angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg, p.o.) 2 h before an injection with the antibody, but not by successive administration of this drug for 1 week from 3 d after the injection of antibody. These results suggested that the enhanced generation of angiotensin II by elevated levels of both renin and its substrate in the early phase of anti-GBM nephritis promotes the evolution of acute nephritis via angiotensin II type 1 receptor.

Topics: Angiotensin Receptor Antagonists; Angiotensinogen; Animals; Antibodies; Basement Membrane; Benzimidazoles; Biphenyl Compounds; Glomerular Mesangium; Glomerulonephritis; Liver; Male; Nephrotic Syndrome; Rats; Rats, Sprague-Dawley; Renin; Renin-Angiotensin System; RNA, Messenger; Tetrazoles

Puromycin aminonucleoside (PAN)-nephrotic rats show high plasma renin, low plasma angiotensinogen (Angt), and increased urinary excretion of renin and Angt. In this work, we studied the effect of captopril on urinary excretion of total protein, renin, and Angt for 25 days after PAN injection. Captopril had no effect on total protein urinary excretion; however, captopril did enhance the urinary excretion of renin and did decrease the urinary excretion of Angt. This seems to be due to the fact that captopril magnifies the increase in renin and the decrease in Angt in the plasma of PAN-nephrotic rats.

Topics: Angiotensinogen; Animals; Captopril; Male; Nephrotic Syndrome; Puromycin Aminonucleoside; Rats; Rats, Inbred Strains; Renin

Literature data on renin in the nephrotic syndrome are conflicting: renin values are reported to be elevated as the rule, but sometimes normal or low; data on renin substrate are scanty and pointing to low values. In the present study, plasma renin activity (PRA) and plasma renin substrates (PRS) were measured in 27 episodes of the nephrotic phase in 24 patients with nephrotic syndrome with various lesions. 10 patients were reinvestigated after remission; 1 patient could be followed during development of the edema phase as well as during prednisone-induced remission. During the nephrotic phase, PRS was suppressed in 8%, normal in 44 and elevated in 48%, while PRA was suppressed in 41%, normal in 48 and elevated in 11% of the patients. After remission, PRA increased in 70% and PRS decreased in 20 and increased in 50% of the cases. The purpose of this study was to investigate PRA and PRS in nephrotic patients; it is concluded that low PRS and high PRA are not as characteristic for the nephrotic syndrome as they are generally thought to be.

Topics: Adult; Angiotensinogen; Angiotensins; Female; Humans; Male; Middle Aged; Nephrotic Syndrome; Prednisone; Renin