Interactions between Angiotensin ll and Atrial Natriuretic Peptide in Renomedullary Interstitial Cells: The Role of Neutral Endopeptidase
- 1 June 2006
- journal article
- Published by S. Karger AG in Nephron Physiology
- Vol. 103 (3), p149-p156
- https://doi.org/10.1159/000092457
Abstract
Neutral endopeptidase (NEP) inhibition attenuates renal damage in the diabetic kidney, but little is known about the mechanisms of this renoprotective effect.We examined the interaction between angiotensin II (Ang II) and atrial natriuretic peptide (ANP) under low (5 mM) and high (30 mM) glucose conditions, on cell proliferation and extracellular matrix (ECM) synthesis in renomedullary interstitial cells (RMICs) derived from wild-type (WT) and NEP-deficient (NEP-) mice.Under high glucose conditions, Ang II (10(-6)M) increased cell proliferation (control, 174.3 +/- 16.9; Ang II, 846.3 +/- 91.0 cpm/well) and ECM synthesis (control, 22.3 +/- 3.1; Ang II, 79.0 +/- 9.6 cpm/cell) in RMICs derived from WT and NEP- mice to a similar extent. ANP (10(-7)M) reduced Ang II-induced cell proliferation and ECM synthesis in RMICs derived from both strains, but more efficiently in RMICs derived from NEP- mice. The Ang II-induced cell proliferation and ECM synthesis was attenuated with AT1 receptor blockade, but more efficiently in RMICs-derived NEP- mice.This data shows that ANP and AT1 receptor blockade attenuate Ang II-induced RMIC proliferation and ECM synthesis more efficiently in the absence of NEP. These results support the concept that NEP inhibition is beneficial in attenuating abnormal cell growth and ECM metabolism associated with diabetic nephropathy.Keywords
This publication has 31 references indexed in Scilit:
- Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: Pathophysiology and indicationsKidney International, 2005
- RENAL RESPONSES TO ATRIAL NATRIURETIC PEPTIDE ARE PRESERVED IN BILATERAL URETERAL OBSTRUCTION AND AUGMENTED BY NEUTRAL ENDOPEPTIDASE INHIBITIONJournal of Urology, 2005
- Relation of ANP and BNP to their N-terminal fragments in fetal circulation: evidence for enhanced neutral endopeptidase activity and resistance of BNP to neutral endopeptidase in the fetusBJOG: An International Journal of Obstetrics and Gynaecology, 2004
- Biochemical analysis of neutral endopeptidase activity reveals independent catabolism of atrial and brain natriuretic peptideBiological Chemistry, 2004
- Differential tissue and enzyme inhibitory effects of the vasopeptidase inhibitor omapatrilat in the ratClinical Science, 2003
- Transformation of interstitial fibroblasts and tubulointerstitial fibrosis in diabetic nephropathyMedical Molecular Morphology, 2002
- High glucose down-regulates angiotensin II binding via the PKC-MAPK-cPLA2 signal cascade in renal proximal tubule cellsKidney International, 2002
- Vasopeptidase inhibition attenuates the progression of renal injury in subtotal nephrectomized ratsKidney International, 2001
- Natriuretic Peptide Receptor-A Negatively Regulates Mitogen-Activated Protein Kinase and Proliferation of Mesangial Cells: Role of cGMP-Dependent Protein KinaseBiochemical and Biophysical Research Communications, 2000
- Angiotensin II inhibits growth of cultured embryonic renomedullary interstitial cells through the AT2 receptorKidney International, 1998