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Targeted deletion of angiotensin II type 1A receptor does not protect mice from progressive nephropathy of overload proteinuria.

Publication ,  Journal Article
Benigni, A; Corna, D; Zoja, C; Longaretti, L; Gagliardini, E; Perico, N; Coffman, TM; Remuzzi, G
Published in: J Am Soc Nephrol
October 2004

In experimental and human renal diseases, progression is limited by angiotensin-converting enzyme inhibitors. Whether renoprotection was due to their capacity of reducing proinflammatory and profibrotic effects of angiotensin II (Ang II) or limiting proteinuria and its long term toxicity is debated. For dissecting the relative contribution of Ang II and proteinuria to chronic renal damage, the protein-overload proteinuria model was used in genetically modified mice lacking the major isoform of murine AT1 receptor (AT1A). Uninephrectomized AT1A+/+ and -/- mice received a daily injection of BSA or saline for 4 or 11 wk. AT1A-/-BSA mice acquired a renal phenotype of proteinuria and renal glomerular and tubulointerstitial lesions, albeit attenuated with respect to AT1A+/+BSA. Administration of the calcium channel blocker lacidipine to reduce BP of AT1A+/+BSA mice to levels of AT1A-/-BSA translated into comparable values of protein excretion rate and glomerular and tubulointerstitial injury in both strains. These results confirm that the toxic effect of protein trafficking on renal disease progression is not necessarily dependent on Ang II to the extent that targeted deletion of AT1A does not prevent disease progression. A role of Ang II via AT1B or AT2 receptors is still a possibility that cannot be ruled out by the present experimental approach. These findings provide a clear rationale for specifically targeting proteinuria in pharmacologic interventions of chronic nephropathies.

Duke Scholars

Published In

J Am Soc Nephrol

DOI

ISSN

1046-6673

Publication Date

October 2004

Volume

15

Issue

10

Start / End Page

2666 / 2674

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Sensitivity and Specificity
  • Reverse Transcriptase Polymerase Chain Reaction
  • Renin-Angiotensin System
  • Receptor, Angiotensin, Type 2
  • Proteinuria
  • Probability
  • Photomicrography
  • Molecular Sequence Data
  • Mice, Inbred C57BL
 

Citation

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Benigni, A., Corna, D., Zoja, C., Longaretti, L., Gagliardini, E., Perico, N., … Remuzzi, G. (2004). Targeted deletion of angiotensin II type 1A receptor does not protect mice from progressive nephropathy of overload proteinuria. J Am Soc Nephrol, 15(10), 2666–2674. https://doi.org/10.1097/01.ASN.0000141465.81556.D2
Benigni, Ariela, Daniela Corna, Carla Zoja, Lorena Longaretti, Elena Gagliardini, Norberto Perico, Thomas M. Coffman, and Giuseppe Remuzzi. “Targeted deletion of angiotensin II type 1A receptor does not protect mice from progressive nephropathy of overload proteinuria.J Am Soc Nephrol 15, no. 10 (October 2004): 2666–74. https://doi.org/10.1097/01.ASN.0000141465.81556.D2.
Benigni A, Corna D, Zoja C, Longaretti L, Gagliardini E, Perico N, et al. Targeted deletion of angiotensin II type 1A receptor does not protect mice from progressive nephropathy of overload proteinuria. J Am Soc Nephrol. 2004 Oct;15(10):2666–74.
Benigni, Ariela, et al. “Targeted deletion of angiotensin II type 1A receptor does not protect mice from progressive nephropathy of overload proteinuria.J Am Soc Nephrol, vol. 15, no. 10, Oct. 2004, pp. 2666–74. Pubmed, doi:10.1097/01.ASN.0000141465.81556.D2.
Benigni A, Corna D, Zoja C, Longaretti L, Gagliardini E, Perico N, Coffman TM, Remuzzi G. Targeted deletion of angiotensin II type 1A receptor does not protect mice from progressive nephropathy of overload proteinuria. J Am Soc Nephrol. 2004 Oct;15(10):2666–2674.

Published In

J Am Soc Nephrol

DOI

ISSN

1046-6673

Publication Date

October 2004

Volume

15

Issue

10

Start / End Page

2666 / 2674

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Sensitivity and Specificity
  • Reverse Transcriptase Polymerase Chain Reaction
  • Renin-Angiotensin System
  • Receptor, Angiotensin, Type 2
  • Proteinuria
  • Probability
  • Photomicrography
  • Molecular Sequence Data
  • Mice, Inbred C57BL