ACE inhibition modulates transforming growth factor-? receptors in the young rat

Abstract

The renin-angiotensin system plays an important role in renal growth and development. Exposure of the neonate to angiotensin converting enzyme (ACE) inhibitors increases mortality and results in growth retardation and abnormal renal development. It has been demonstrated that ACE inhibition in the developing kidney reduces the renal expression of growth factors, which may account for renal growth impairment. This study was designed to investigate the relationship between renal growth impairment and the expression of transforming growth factor-beta1 (TGF-beta1), TGF-beta receptor I [TbetaRI, activin-like kinase (ALK)-1 and ALK-5], and TGF-beta receptor II (TbetaRII). Newborn rat pups were treated with enalapril (30 mg/kg per day) or vehicle for 7 days, and kidneys were removed for Western blotting of TGF-beta1, ALK-1, ALK-5, and TbetaRII, and for RT-PCR of ALK-5 and TbetaRII. TGF-beta1, ALK-1, ALK-5, and TbetaRII were also detected by immunohistochemistry. Enalapril treatment resulted in an increased mortality (30.4%) by day 7, and reduced body weight and kidney weight ( P<0.05 versus vehicle). Enalapril decreased renal TGF-beta1, ALK-1, and ALK-5 protein expression ( P<0.05). Also, enalapril decreased ALK-5 mRNA expression ( P<0.05). TbetaRII expression was not changed by enalapril treatment. These results indicate that ACE inhibition in the developing kidney decreases TGF-beta1, ALK-1, and ALK-5 expression, which may account for renal growth impairment. TbetaRII may not be modulated by ACE inhibition in the developing kidney.

Endothelin A Receptor Blockade Influences Apoptosis and Cellular Proliferation in the Developing Rat Kidney

“…Our previous studies demonstrated that ACE inhibition by enalapril decreased cellular proliferation in the developing rat kidney. The PCNA-positive proliferating cells were also decreased significantly in the same cortical tubular epithelial cells (12, 15). …”

“…Ang II inhibition by angiotensin converting enzyme (ACE) inhibitor in the developing rat kidney decreases the cellular proliferation and increases apoptosis, and this may account for neonatal renal growth impairment (7, 8, 12-15). These results suggest that the RAS is necessary for normal renal growth and development.…”

Spontaneous Epiretinal Membrane Resolution and Angiotensin Receptor Blockers: Case Observation, Literature Review and Perspectives

“…It has been previously reported that ERMs can spontaneously resolve in cases of PVD occurrence, and this may happen when the ERM's adhesion to the posterior hyaloid membrane is stronger than its adhesion to the underlying ILM [76][77][78][79]. Since our patient was known to have an already complete PVD prior to the diagnosis of ERM and the intake of ARBs (candesartan) was the only evident discriminating factor that could have led to the spontaneous resolution of ERM, we hypothesize a molecular mechanism through which the fibrosis constituting the ERM could been affected and resolved by the molecular mechanism of ARBs (Figure 3).…”

Renin-Angiotensin System - Considerations for Hypertension and Kidney

“…Whether Ang II either mediates proliferation or rather hypertrophy depends on the renal cell type. All components of the RAS are developmentally regulated in renal organogenesis, and blocking the RAS in the developing kidney shows severe renal abnormalities and abnormal cellular turnover18). Ang II-induced growth effects are also implicated in the development of glomerulosclerosis and tubulointerstitial fibrosis and antagonizing these effects is a primary target of renoprotection modality in clinical nephrology.…”