The paradox of the renin-angiotensin system in chronic renal disease

Rosenberg, Mark E.; Smith, Lawrence J.; Correa‐Rotter, Ricardo; Hostetter, Thomas H.

doi:10.1038/ki.1994.52

Cited by 153 publications

(103 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These growth processes precede the later development of glomerulosclerosis and tubulointerstitial fibrosis. However, in some studies ACE inhibitors have failed to ameliorate the progressive renal impairment (22), and the observed changes of ACE activity in circulation and local tissues have not always been the same (10,22). We therefore concluded that it was more important to examine changes in local Ang II in the kidneys.…”

Section: Discussionmentioning

confidence: 99%

Renal Protective Effects of Blocking the Intrarenal Renin-Angiotensin System.

Zhou

et al. 1999

Hypertens Res

View full text Add to dashboard Cite

It has been well demonstrated that angiotensin-converting enzyme inhibitors (ACEIs) can retard the progression of renal failure and kidney sclerosis in patients and animal models with glomerular diseases. The aim of this study was to observe the influences of ACEI on intrarenal Ang II and TGFi81 local formation and their relation to renal protective effects. Experimental glomerulosclerosis with nephrotic syndrome was induced in unilateral nephrectomized rats with repeated injections of adriamycin. Rats were randomly divided into three groups: 1) a sham-operated control group (n = 8); 2) an NS group treated with ACE! (benazepril 4 mg/kg/d) (n =10), and 3) an NS group not treated (n =10). After 8 wk, serum, urine and renal tissue were collected for study. ACE activity and Ang II concentration in renal tissue were measured by colorimetry and radioimmunoassay, respectively. Immunohistochemistry staining was employed for transforming growth factor-,81 (TGF/91) and extracellular matrix (ECM) examination. .01 in all cases). In the ACEI treated group, these histologic benefits coincided with a reduced expression of TGFi91 in both tubular cells and sclerosed glomeruli in protein as well as mRNA level. These findings provide further evidence that ACE! (benazepril) can prevent the progression of renal damage in both the function and morphologic changes which associated with a down-regulation of intrarenal Ang II level through the relative inhibition of renal ACE activity. The blocking of the Intrarenal renin angiotensin system (RAS) might contribute to the inhibition of TGFj91 local formation and the TGFi91-mediated ECM accumulation that are related to the renal protective effects of ACE!. (Hypertens Res 1999; 22: 223-228)

show abstract

Section: Discussionmentioning

confidence: 99%

Renal Protective Effects of Blocking the Intrarenal Renin-Angiotensin System.

Zhou

et al. 1999

Hypertens Res

View full text Add to dashboard Cite

show abstract

“…1-4 These benefits of ACE inhibition and ATR blockade are probably attributed to the suppression of intrarenal angiotensin II concentrations and the changes that follow as a consequence. 4,5 Recent clinical and experimental studies have demonstrated that elevated plasma aldosterone may also contribute to the progression of cardiac and renal disease. 6,7 Greene et al 8 demonstrated a significant suppression of hyperaldosteronism and a marked attenuation of proteinuria, hypertension, and glomerulosclerosis in a remnant kidney model using rats that were treated with enalapril and losartan.…”

mentioning

confidence: 99%

Aldosterone-Stimulated SGK1 Activity Mediates Profibrotic Signaling in the Mesangium

Terada

Kuwana²,

Kobayashi³

et al. 2008

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Several recent reports support the hypothesis that aldosterone contributes to the progression of renal injury. Mineralocorticoids increase the expression of serum-and glucocorticoid-inducible protein kinase 1 (SGK1), which is upregulated in several fibrotic diseases. It was hypothesized that SGK1 may mediate the effects of aldosterone on glomerular fibrosis and inflammation. In primary cultures of rat mesangial cells, aldosterone stimulated the expression, phosphorylation, and kinase activity of SGK1, as well as SGK1-dependent NF-B activity. Furthermore, aldosterone augmented the promoter activity and protein expression of intercellular adhesion molecule-1 (ICAM-1), which modulates the inflammatory response, and the profibrotic cytokine connective tissue growth factor (CTGF) in an SGK1-and NF-Bdependent manner. Similar to the in vitro results, uninephrectomized rats that were treated with aldosterone demonstrated increased glomerular expression of SGK1, ICAM-1, and CTGF proteins than untreated rats; these changes were accompanied by hypertension, glomerulosclerosis, and inflammation. In conclusion, these findings suggest that aldosterone stimulates ICAM-1 and CTGF transcription via the activation of SGK1 and NF-B, effects that may contribute to the progression of aldosteroneinduced mesangial fibrosis and inflammation. Accumulating evidence suggests that angiotensinconverting enzyme (ACE) inhibition or angiotensin II receptor (ATR) blockade attenuates the decline in renal function and structural damage in various kidney diseases. 1-4 These benefits of ACE inhibition and ATR blockade are probably attributed to the suppression of intrarenal angiotensin II concentrations and the changes that follow as a consequence. 4,5 Recent clinical and experimental studies have demonstrated that elevated plasma aldosterone may also contribute to the progression of cardiac and renal disease. 6,7 Greene et al. 8 demonstrated a significant suppression of hyperaldosteronism and a marked attenuation of proteinuria, hypertension, and glomerulosclerosis in a remnant kidney model using rats that were treated with enalapril and losartan. Similarly, Rocha et al. 9 demonstrated the renoprotective effects of eplerenone and spironolactone in an aldosterone-stimulated rat model. Chrysostomou and Becker 7 found that the addition of spironolactone to ACE inhibitors markedly reduced the urinary excretion rate of protein in patients with chronic renal failure without exerting hemodynamic effects. All of these studies strongly suggest that aldosterone is involved in the pathogenesis of renal injury.Our group recently revealed that aldosterone stimulates the mitogen-activated protein kinase

show abstract

“…In the remnant kidney model, angiotensin II generated in ischemic areas may participate in renal injury as an autocrine and/or paracrine growth factor. Hostetter and his associates studied the importance of the renin-angiotensin-aldosterone (RAS) axis in the rat remnant kidney (16)(17)(18) and reported that renin and renin mRNA derived from scar-adjacent tissue were increased (19). This finding may arise from the relative hypoperfusuin of those nephrons in a "watershed" zone, as suggested by Meyer and Rennke (20).…”

Section: Introductionmentioning

confidence: 67%