Angiotensin Type 1 Receptor Blocker Restores Podocyte Potential to Promote Glomerular Endothelial Cell Growth

Liang, Xiaowen; Li, Jun; Naito, Takashi; Wang, Yihan; Madaio, Michael P.; Zent, Roy; Pozzi, Ambra; Fogo, Agnes B.

doi:10.1681/asn.2005020205

Cited by 54 publications

(41 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…37 AT 1 receptor antagonist treatment ameliorated proteinuria by preventing a reduction in the functional molecules of the slit diaphragm. 38,39 All these considerations provide support for our hypothesis that the proteinuria induced by prenatal exposure to LPS in this study may occur through the activation of intrarenal RAS.…”

Section: Discussionsupporting

confidence: 79%

Prenatal exposure to lipopolysaccharide alters the intrarenal renin–angiotensin system and renal damage in offspring rats

et al. 2009

View full text Add to dashboard Cite

Prenatal exposure to inflammation produces offspring that are hypertensive in adulthood. This study explored alterations of the renin-angiotensin system (RAS) during the development of hypertension induced by prenatal exposure to lipopolysaccharide (LPS). In addition, the effects of an inhibitor of the nuclear transcription factor (NF)-jB (pyrrolidine dithiocarbamate, PDTC) on this process were assessed. Pregnant rats were randomly divided into four groups (n¼8): a control group, an LPS group, a PDTC group and an LPS+PDTC group. The rats in these groups were intraperitoneally administered vehicle, 0.79 mg kg À1 LPS, 100 mg kg À1 PDTC or LPS plus PDTC, respectively. LPS was given on the 8th, 10th and 12th days, whereas PDTC was given from the 8th to the 14th day during gestation. At various ages from day 1 to 25 weeks, plasma renin activity, plasma angiotensin II (Ang II) levels, renal function, glomerular number, mRNA expression levels of renal cortex renin and angiotensin-converting enzyme (ACE), the number of Ang II-positive cells and NF-jB activation were determined. The results showed that prenatal exposure to LPS resulted in significantly lower glomerular numbers and creatinine clearance rates and higher urinary protein and renal cortex ACE mRNA expression in adult offspring. Prenatal LPS also decreased the renal cortex renin mRNA expression and the number of Ang II-positive cells in offspring at 1 day of age, but these increased at 7, 16 and 25 weeks, whereas the plasma renin activity and Ang II concentration remained unchanged. Simultaneously, PDTC treatment markedly reversed the action of LPS. In conclusion, prenatal exposure to LPS resulted in alteration of the intrarenal RAS and renal damage in adult offspring rats. INTRODUCTIONThe effects of hypertension on the cardiovascular and renal systems are of major concern due to its morbidity and mortality. Though many efforts have been made to understand the pathophysiology of hypertension, it is still unclear because of its complexity. 1 A growing body of evidence indicates that hypertension is an inflammatory state wherein proinflammatory cytokines, such as tumor necrosis factor-a and interleukin-6, contribute to the hypertensive effect. 2-5 Angiotensin II (Ang II), the major biologically active component of the reninangiotensin system (RAS), not only induces vasoconstriction, aldosterone release and sodium reabsorption by the nephron, but is also intricately interrelated with inflammation. Furthermore, the association of Ang II and inflammation induces an amplification process that involves oxidative stress and proinflammatory transcription factors, leading to progressive vascular injury 6 and having an important role in the development of hypertension and target organ damage. 2 It has been shown in our laboratory that maternal exposure to lipopolysaccharide (LPS) results in hypertension in offspring rats. 7

show abstract

Section: Discussionsupporting

confidence: 79%

Prenatal exposure to lipopolysaccharide alters the intrarenal renin–angiotensin system and renal damage in offspring rats

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In contrast, when injured podocytes also were treated with ARB, VEGF and angiopoietin-1 were restored, and this supernatant supported increased growth and branching of glomerular endothelial cells. 14 The current data support that ARB induces capillary growth in vivo as well. We hypothesize that this effect may be mediated in part by effects on podocytes.…”

Section: Discussionsupporting

confidence: 77%

“…Our in vitro data in cultured glomerular endothelial cells suggest that capillary growth could be achieved with high-dose ARB, perhaps contributed to by improved podocyte survival induced by ARB and/or effects directly on the endothelium. 14 We therefore aimed to determine whether this mechanism of angiogenesis was present in vivo in ARB-induced regression of sclerosis. Three-dimensional confocal images were analyzed by graph theory analysis to explore the branching pattern of the capillary network in normal glomeruli versus glomeruli with sclerosis induced by 5/6 nephrectomy and compared with glomeruli in which ARB induced regression of sclerosis.…”

mentioning

confidence: 99%

Increased Capillary Branching Contributes to Angiotensin Type 1 Receptor Blocker (ARB)–Induced Regression of Sclerosis

Scruggs

Zuo

Donnert

et al. 2011

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Chronic kidney disease is characterized by progressive glomerulosclerosis and tubulointerstitial fibrosis. High-dose angiotensin type 1 receptor blocker (ARB) or angiotensin-converting enzyme inhibitor can induce regression of existing glomerulosclerosis, at least in part by decreasing matrix accumulation. However, the potential mechanisms of remodeling of capillary loops remain obscure. This study aimed to determine whether capillary branching was augmented in glomeruli with ARB-induced regression of sclerosis. Three-dimensional confocal images were assessed by graph theory analysis to explore the topology of the glomerular capillary network. Compared with normal glomeruli, glomeruli of rats with progressive sclerosis were enlarged but had a significantly reduced number of capillary segments and capillary branch points and decreased complexity of the glomerular network. In contrast, in rats with regression of sclerosis induced by ARB, glomerular enlargement was due to a significantly increased number of glomerular capillary segments and capillary branch points and restored complexity of the capillary network. These data support the theory that capillary growth contributes to regression of sclerosis and is mediated at least in part by ARB-induced increased complexity and branching of capillary segments.

show abstract

“…Both receptor subtypes have been demonstrated in rat GECs (17). Ang II exerts most of its already well-defined physiologic and pathophysiologic actions through AT 1 receptors (18).…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Angiotensin Type 1 Receptor Blocker Restores Podocyte Potential to Promote Glomerular Endothelial Cell Growth

Cited by 54 publications

References 54 publications

Prenatal exposure to lipopolysaccharide alters the intrarenal renin–angiotensin system and renal damage in offspring rats

Prenatal exposure to lipopolysaccharide alters the intrarenal renin–angiotensin system and renal damage in offspring rats

Increased Capillary Branching Contributes to Angiotensin Type 1 Receptor Blocker (ARB)–Induced Regression of Sclerosis

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

Contact Info

Product

Resources

About