Young Scholars Award Lecture: Intratubular Angiotensinogen in Hypertension and Kidney Diseases

Kobori, Hiroyuki; Ozawa, Yuri; Suzaki, Yuki; Prieto-Carrasquero, Minolfa C.; Nishiyama, Akira; Tanaka, Shōji; Cohen, Eric P.; Navar, L. Gabriel

doi:10.1016/j.amjhyper.2005.11.014

Cited by 89 publications

(89 citation statements)

References 111 publications

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“…Activation of the intrarenal renin-angiotensin system is a characteristic feature of the development and progression of chronic kidney disease (1). Angiotensin II (Ang II), the main effector of the renin-angiotensin system, is implicated in the pathogenesis of renal diseases (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…Angiotensin II (Ang II), the main effector of the renin-angiotensin system, is implicated in the pathogenesis of renal diseases (2,3). Ang II initiates its effects by interacting with at least two pharmacologically distinct subtypes of cell surface receptors, AT 1 and AT 2 . The major functions of Ang II in the cardiovascular system are mediated by the AT 1 receptor (4,5).…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin II stimulates MCP-1 production in rat glomerular endothelial cells via NAD(P)H oxidase-dependent nuclear factor-kappa B signaling

Pan

Yang

Cheng

2009

Braz J Med Biol Res

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Angiotensin II (Ang II) plays a crucial role in the pathogenesis of renal diseases. The objective of the present study was to investigate the possible inflammatory effect of Ang II on glomerular endothelial cells and the underlying mechanism. We isolated and characterized primary cultures of rat glomerular endothelial cells (GECs) and observed that Ang II induced the synthesis of monocyte chemoattractant protein-1 (MCP-1) in GECs as demonstrated by Western blot. Ang II stimulation, at concentrations ranging from 0.1 to 10 μm, of rat GECs induced a rapid increase in the generation of reactive oxygen species as indicated by laser fluoroscopy. The level of p47 phox protein, an NAD(P)H oxidase subunit, was also increased by Ang II treatment. These effects of Ang II on GECs were all reduced by diphenyleneiodonium (1.0 μm), an NAD(P)H oxidase inhibitor. Ang II stimulation also promoted the activation of nuclear factor-kappa B (NF-κB). Telmisartan (1.0 μm), an AT 1 receptor blocker, blocked all the effects of Ang II on rat GECs. These data suggest that the inhibition of NAD(P)H oxidase-dependent NF-κB signaling reduces the increase in MCP-1 production by GECs induced by Ang II. This may provide a mechanistic basis for the benefits of selective AT 1 blockade in dealing with chronic renal disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Angiotensin II stimulates MCP-1 production in rat glomerular endothelial cells via NAD(P)H oxidase-dependent nuclear factor-kappa B signaling

Pan

Yang

Cheng

2009

Braz J Med Biol Res

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“…This may be explained by an intrarenal system for renin (27), angiotensinogen (28), Ang II (29), and ACE (30) that is under regulation separate from juxtaglomerular renin release (28,30). Administration of an ACE inhibitor or an Ang II receptor blocker (ARB) to STZ-induced diabetic rats or patients with type 2 diabetes reduces markers of inflammation, oxidative stress, and albuminuria, independent of blood pressure or creatinine clearance (31,32).…”

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confidence: 99%

Expression of NG,NG-Dimethylarginine Dimethylaminohydrolase and Protein Arginine N-Methyltransferase Isoforms in Diabetic Rat Kidney

et al. 2008

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OBJECTIVE-The nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) is generated by protein arginine N-methyltransferase (PRMT)-1 and is metabolized by N G ,N Gdimethylarginine dimethylaminohydrolase (DDAH). We tested the hypothesis that increased serum ADMA (S ADMA ) in the streptozotocin (STZ)-induced diabetic rat model of diabetes is mediated by an angiotensin receptor blocker-sensitive change in DDAH or PRMT expression. RESEARCH DESIGN AND METHODS-Datawere compared from four groups of rats: sham-injected controls, untreated STZ-induced diabetic rats at 4 weeks, STZ-induced diabetic rats administered the angiotensin II (Ang II) receptor blocker telmisartan for 2 weeks, and control rats administered telmisartan for 2 weeks.RESULTS-Immunostaining and Western blotting of microdissected nephron segments localized DDAH I in the proximal tubules and DDAH II in the glomeruli, afferent arterioles, macula densa, and distal nephron. Renal Ang II and S ADMA increased with diabetes but were normalized by 2 weeks of telmisartan. DDAH I expression was decreased in diabetic kidneys, while DDAH II expression was increased. These changes were reversed by telmisartan, which also reduced expression of PRMT-1 and -5. Telmisartan increased expressions of DDAH I but decreased DDAH II in Ang II-stimulated kidney slices ex vivo. CONCLUSIONS-RenalAng II and S ADMA are increased in insulinopenic diabetes. They are normalized by an Ang II receptor blocker, which increases the renal expression of DDAH I, decreases PRMT-1, and increases renal NO metabolites.

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“…he renin-angiotensin system (RAS) plays a fundamental role in the regulation of arterial blood pressure, fluid, and electrolyte homeostasis (1). In the RAS, renin cleaves angiotensinogen to generate angiotensin (Ang) I, Ang-(1-10).…”

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confidence: 99%

Ontogeny of angiotensin-converting enzyme 2

2011

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INTRODUCTION:This study examined the temporal expression of angiotensin (ang)-converting enzyme 2 (ace2) during renal, heart, lung, and brain organogenesis in the mouse. RESULTS: We demonstrate that kidney ace2 mRNa levels are low on embryonic day (e) 12.5, increase fourfold during development, and decline in adulthood. In extrarenal tissues, ace2 mRNa levels are also low during early gestation, increase in perinatal period, and peak in adulthood. The lung shows the highest age-related increase in ace2 mRNa levels followed by the brain, kidney, and heart. ace2 protein levels and enzymatic activity are high in all organs studied during gestation and decline postnatally. ang II decreases ace2 mRNa levels and enzymatic activity in kidneys grown ex vivo. These effects of ang II are blocked by the specific ang II aT 1 receptor (aT 1 R) antagonist candesartan, but not by the aT 2 receptor (aT 2 R) antagonist PD123319. DISCUSSION: We conclude that ACE2 gene and protein expression and enzymatic activity are developmentally regulated in a tissue-specific manner. ang II, acting through aT 1 R, exerts a negative feedback on ace2 during kidney development. We postulate that relatively high ace2 protein levels and enzymatic activity observed during gestation may play a role in kidney, lung, brain, and heart organogenesis.

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Young Scholars Award Lecture: Intratubular Angiotensinogen in Hypertension and Kidney Diseases

Cited by 89 publications

References 111 publications

Angiotensin II stimulates MCP-1 production in rat glomerular endothelial cells via NAD(P)H oxidase-dependent nuclear factor-kappa B signaling

Angiotensin II stimulates MCP-1 production in rat glomerular endothelial cells via NAD(P)H oxidase-dependent nuclear factor-kappa B signaling

Expression of NG,NG-Dimethylarginine Dimethylaminohydrolase and Protein Arginine N-Methyltransferase Isoforms in Diabetic Rat Kidney

Ontogeny of angiotensin-converting enzyme 2

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