Immunocytochemical localization of angiotensinogen in rat liver and kidney

Richoux, J. P.; Cordonnier, J.; Bouhnik, J; Clauser, Éric; Corvol, Pierre; Ménard, Joël; Grignon, G

doi:10.1007/bf00238309

Cited by 92 publications

(67 citation statements)

References 25 publications

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“…47,48,50,52 Proximal tubular cells express mRNA [54][55][56] and protein 53,57 for ACE and Aogen. [58][59][60][61] In vivo evidence that proximal tubular cells may synthesize Ang II has also been reported. 62 The above studies indicate the presence of a functional renal tubular RAAS, which likely has an important function in regulating sodium and fluid balance, and hence BP.…”

Section: Intrarenal Raasmentioning

confidence: 88%

New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal disease

Feldman

2010

Hypertens Res

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The renin-angiotensin-aldosterone system (RAAS) has a central function in the regulation of blood pressure. Aliskiren, the first direct renin inhibitor to be approved for the treatment of hypertension, blocks the RAAS at its point of activation. As renin inhibition acts at the top of the RAAS cascade, this mechanism has been proposed to offer advantages over existing modes of RAAS blockade. The RAAS is also considered to be a major factor in the pathogenesis of many renal diseases, especially diabetic nephropathy (DN), the main cause of end-stage renal disease. Existing therapies to block the RAAS slow the progression of DN, but they do not halt the disease. Therefore, more effective modes of interventions are needed. Studies to determine the efficacy of aliskiren in human renal disease are in progress. This review summarizes in vivo studies in which the efficacy of aliskiren was tested in experimental models of renal disease, and presents in vitro studies that provide insights into the possible mechanisms by which aliskiren confers renoprotection in animals. These works are discussed in the framework of the intrarenal RAAS and suggest that aliskiren may act by unique renoprotective mechanisms. Keywords: aliskiren; kidney; mechanism; nephropathy; renin INTRODUCTIONThe renin-angiotensin-aldosterone system (RAAS) is an ancient pathway 1 that has evolved into a central mechanism by which mammalian blood pressure (BP) and fluid homeostasis are regulated. Research in this field started with the discovery in 1898 by Tigerstedt and Berman 2 that a renal extract when injected into rabbits induced a rapid increase in systemic BP. Subsequent work over many years established the RAAS as a pivotal contributor to cardiorenal diseases. Hence, inhibitors of the middle and distal portions of the RAAS pathway, angiotensin-converting enzyme (ACE) inhibitors (ACEI) and AT 1 receptor blockers, respectively, have become mainstay therapies for treating hypertension. In 2007, aliskiren, the first direct renin inhibitor (DRI), was approved for the treatment of hypertension. This heralded the therapeutic control of BP by inhibiting the RAAS at its first and rate-limiting step. However, RAAS blockade is also effective for treating renal disease 3-6 and the efficacy of aliskiren for this purpose is currently being investigated. Accordingly, the subject of this review is to summarize the preclinical evidence for renoprotection by aliskiren, and to discuss recently published information on the possible mechanism(s) for these benefits. As it is well recognized that there is a tissue as well as circulating RAAS, 7 the preclinical actions of aliskiren will be discussed in the context of the intrarenal RAAS and the potential for its inhibition by aliskiren.

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Section: Intrarenal Raasmentioning

confidence: 88%

New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal disease

Feldman

2010

Hypertens Res

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“…Thus, aside from intrarenal vessels, the renin gene is expressed along the proximal tubule, but not in the collecting duct. Since renin substrate and converting enzyme activity is present in proximal tubule cells (6)(7)(8)(9)(10)(11)(12) Figure 6. Autoradiographs of representative renin and /3-actin PCR from CEI treated series.…”

Section: Discussionmentioning

confidence: 99%

“…Immunocytochemical studies have shown the presence of angiotensinogen in the proximal tubule (6), and angiotensinogen mRNA at this site has been detected by in situ hybridization methods, indicating that the renin substrate is, in fact, synthesized by proximal tubule cells (7,8). There also appears to be an abundance of angiotensin converting enzyme in both the apical and basolateral membranes of the proximal tubule (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Renin and renin mRNA in proximal tubules of the rat kidney.

M¹,

Harris²,

Rose³

et al. 1994

J. Clin. Invest.

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The present study was undertaken to assess the presence of renin enzymatic activity and renin mRNA in proximal tubules of rat kidneys, and to determine the effect of converting enzyme inhibition (CEI) on proximal tubule renin gene expression. Proximal convoluted tubules (PCT), proximal straight tubules (PST), outer medullary collecting ducts (OMCD), and glomeruli (Gloms) were isolated by microdissection. Renin activity was measured in sonicated segments by radioimmunoassay. Renin mRNA levels were assessed using a quantitative PCR. Renin activity in PCT averaged 51± 15 IAGU/mm compared to 405±120 ,uGU/ glomerulus. No measurable renin activity was found in PST and OMCD. Renin activity in both glomeruli and tubules had the same pH optimum, between 7.0 and 7.5. Renin mRNA was consistently detectable in cDNA prepared from PCT and PST, although its abundance per mm tubule was about 1/500th that found in one glomerulus. Renin mRNA was not detectable in OMCD. Tubular renin PCR product identity was confirmed by restriction digestion. CEI administration increased glomerular renin activity and renin mRNA, but not proximal tubular renin. The absence of a stimulatory effect of CEI on proximal tubule renin gene expression suggests the operation of different intracellular signals in control of renin synthesis in the proximal tubule than in the vascular compartment. (J. Clin. Invest. 1994. 94:237-243.)

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“…Although it is difficult to demonstrate angiotensinogen in hepatocytes by immunohistochemistry and to have it found by both in situ hybridization and northern blot analysis, immunohistochemical detection of angiotensinogen has been successfully reported by a few investigators, who treated the rat with bilateral nephrectomy or colchicin injections (MORRIS et al, 1979;RICHoUx et al, 1983;CAMPBELL and HABENER, 1987;GAILLARD-SANCHEZ et al, 1990). Angiotensinogen in human liver is synthesized as a precursor composed of 485 amino acid residures, cleaved into signal peptide composed of 33 amino acid residues and glycosylated angiotensinogen, and then immediately released by a possibly constitutive pathway (DOOLITTLE, 1983;CLAUSER et al, 1989).…”

Section: Circulating Renin-angiotensin Systemmentioning

confidence: 99%

Local Renin-Angiotensin System: Especially in Coagulating Glands of Mice.

Kon

1996

Archives of Histology and Cytology

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Immunocytochemical localization of angiotensinogen in rat liver and kidney

Cited by 92 publications

References 25 publications

New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal disease

New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal disease

Renin and renin mRNA in proximal tubules of the rat kidney.

Local Renin-Angiotensin System: Especially in Coagulating Glands of Mice.

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