The Aggravating Mechanisms of Aldosterone on Kidney Fibrosis

Remuzzi, Giuseppe; Cattaneo, Dario; Perico, Norberto

doi:10.1681/asn.2007101079

Cited by 99 publications

(86 citation statements)

References 35 publications

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“…131 Local renal aldosterone production in the renal cortex has been demonstrated in rodent models stimulated by Ang II, decreased sodium intake and hyperglycemia with the mineralocorticoid receptor identified not only in the distal tubule but also in pre-glomerular vasculature, mesangial cells and on fibroblasts. 132 In vitro studies have shown that mesangial cells significantly increase production of TGFβ and fibronectin in response to aldosterone, an effect which can be mitigated by the aldosterone antagonist, spironolactone. 133 In vivo aldosterone infusion in rats significantly increases urinary TGFβ concentration and rats that have undergone uninephrectomy and receive aldosterone at the same time as AT1 blockade, showed increased expression of TGFβ and collagen, supporting that aldosterone is an independent pro-fibrotic mediator.…”

Section: Activation Of the Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

“…133 In vivo aldosterone infusion in rats significantly increases urinary TGFβ concentration and rats that have undergone uninephrectomy and receive aldosterone at the same time as AT1 blockade, showed increased expression of TGFβ and collagen, supporting that aldosterone is an independent pro-fibrotic mediator. 132,134,135 Aldosterone has also been shown to increase expression of CTGF and to increase production of ROS and inflammatory mediators such as osteopontin, IL6 and IL1. 136,137 Aldosterone may also promote fibroblast growth and proliferation and increase expression of PAI-1, which promotes ECM accumulation.…”

Section: Activation Of the Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

“…136,137 Aldosterone may also promote fibroblast growth and proliferation and increase expression of PAI-1, which promotes ECM accumulation. 131,132 Numerous in vivo models of aldosterone inhibition using either the non-selective agent, spironolactone, or the specific aldosterone receptor inhibitor, eplenerone, demonstrate reduction in glomerulosclerosis and interstitial fibrosis. 132 In human medicine, clinical evidence of the role of RAAS in progression of CKD comes from studies that have evaluated RAAS blockade.…”

Section: Activation Of the Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

“…131,132 Numerous in vivo models of aldosterone inhibition using either the non-selective agent, spironolactone, or the specific aldosterone receptor inhibitor, eplenerone, demonstrate reduction in glomerulosclerosis and interstitial fibrosis. 132 In human medicine, clinical evidence of the role of RAAS in progression of CKD comes from studies that have evaluated RAAS blockade. Studies investigating both ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) show improved outcome when these agents are administered for both diabetic and non-diabetic related CKD.…”

Section: Activation Of the Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

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Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

Jepson

2016

Veterinary Clinics of North America: Small Animal Practice

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Abstract:In cats with chronic kidney disease (CKD), the most common histopathological finding is tubulointerstitial inflammation and fibrosis. However, these changes reflect a non-specific response of the kidney to any inciting injury. The risk of development of CKD in a patient is likely to reflect genetic predispositions, ageing, environmental and individual factors that influence decline in renal function over the course of a cat's life. However, there is still relatively little information about exactly which risk factors predispose a cat to develop CKD and these will be explored. Whilst many cats diagnosed with CKD have stable disease for many years, some cats show overtly progressive disease.

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Section: Activation Of the Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

Section: Activation Of the Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

Section: Activation Of the Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

Section: Activation Of the Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

See 2 more Smart Citations

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

Jepson

2016

Veterinary Clinics of North America: Small Animal Practice

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“…ATII and aldosterone stimulate the proliferation of hepatic stellate cells (HSC) and collagen synthesis, and are involved in the generation of reactive oxygen species (ROS) both in vitro and in vivo (6)(7)(8). ATII type 1 receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) have been reported to prevent the development of hepatic fibrosis in numerous animal (6)(7)(8)(9)(10)(11)(12) and human (13)(14)(15) studies. However, only a few studies examining the antifibrotic effects of aldosterone blockers have been reported to date.…”

Section: Introductionmentioning

confidence: 99%

The effects of the selective mineralocorticoid receptor antagonist eplerenone on hepatic fibrosis induced by bile duct ligation in rat

Matono

Koda²,

Tokunaga³

et al. 2010

Int J Mol Med

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Abstract. The aim of this study was to examine the effects of eplerenone on hepatic fibrosis induced by bile duct ligation (BDL) in rat. Low-(1.0 mg/kg body weight, BW) and high-(4.0 mg/kg BW) dose eplerenone was administered orally for 21 days immediately following BDL. Fibrosis was assessed by measuring the fibrotic area after Sirius red staining. Immunostaining for ·-smooth muscle actin (SMA), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) was also carried out. Gene expression levels of procollagen-I, transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), tissue inhibitor of metalloproteinases-1 (TIMP-1) and matrix metalloproteinase-13 (MMP-13) in the liver were examined by real-time reverse transcriptase polymerase chain reaction. Plasma angiotensin II (ATII) concentration was measured via radioimmunoassay. The area of hepatic fibrosis and ·-SMA positivity in the high-dose group was significantly decreased compared with that in the BDL group, but not in the low-dose group. 8-OHdG-positive cells in the low-and high-dose groups were significantly decreased compared with those in the BDL group. Immunostaining of 4-HNE in the high-dose group was significantly lower compared with that in the BDL group. Furthermore, TIMP-1 mRNA levels in the low-and high-dose groups were lower than that in the BDL group. The expression of TGF-ß1, CTGF, procollagen-1 and MMP-13 showed no differences. Plasma ATII concentration in the high-dose group was significantly decreased. Eplerenone attenuated the development of BDL-induced hepatic fibrosis by reducing oxidative stress, suppressing activated hepatic stellate cells and decreasing plasma ATII levels. Eplerenone may prove useful as an alternative treatment for antifibrosis therapy. IntroductionAngiotensin II (ATII) and aldosterone are the main effector peptides of the renin-angiotensin-aldosterone system (RAAS) and are known to be important mediators of hepatic fibrosis and portal hypertension (1-5). ATII and aldosterone stimulate the proliferation of hepatic stellate cells (HSC) and collagen synthesis, and are involved in the generation of reactive oxygen species (ROS) both in vitro and in vivo (6-8). ATII type 1 receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) have been reported to prevent the development of hepatic fibrosis in numerous animal (6-12) and human (13-15) studies. However, only a few studies examining the antifibrotic effects of aldosterone blockers have been reported to date. The results arising from these studies have proven to be controversial (1,2,5). Fujisawa et al (5) reported that spironolactone prevented pig serum-induced hepatic fibrosis in rats, while Oberti et al (2) showed that spironolactone did not produce any anti-fibrotic effects during bile duct ligation (BDL)-induced hepatic fibrosis.The novel aldosterone blocker eplerenone has been shown to exhibit a high specificity for mineralocorticoid receptors (16,17). While the efficacy and safety of eplerenone in the treatment of hype...

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Aging and Remodeling of the RAS and RAAS and Related Pathways: Implications for Heart Failure Therapy

Jugdutt

2014

Aging and Heart Failure

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The Aggravating Mechanisms of Aldosterone on Kidney Fibrosis

Cited by 99 publications

References 35 publications

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

The effects of the selective mineralocorticoid receptor antagonist eplerenone on hepatic fibrosis induced by bile duct ligation in rat

Aging and Remodeling of the RAS and RAAS and Related Pathways: Implications for Heart Failure Therapy

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