Abstract 17797: Protective Role of Angiotensin-(1-7) Receptor Mas on Kidney Fibrosis
Angiotensin (Ang) II is involved in inflammatory and fibrotic mechanisms of cardiovascular and renal diseases. Ang-(1-7) counterbalances most of the Ang II pathophysiological effects. However, a protective role for Ang-(1-7) in kidney fibrosis remains speculative. To evaluate the role of Ang-(1-7) receptor Mas on pathophysiological mechanisms of kidney fibrosis we used a distinct genetic background of Mas-knockout mice (FVB/N MasKO). Urine and plasma samples were collected for measuring renal function parameters. Kidneys were harvested for histology, confocal immunofluorescence of matrix proteins, RT-PCR of AT1 receptor and TGF-beta and TUNEL apoptosis. Compared with wild-type controls, MasKO mice have reduced 24h-urine volume (0.75±0.15 vs. 1.51±0.33mL p<0.05) and sodium fractional excretion (1.09±0.21 vs. 2.16±0.45% p<0.05), without changes in osmolal and free-water clearances. The 1.8-fold higher creatinine clearance (7.11±1.25 vs. 3.92±0.48µL.min.g-1 p<0.05) and the 2.9-fold increase in albuminuria (3.42±0.56 vs. 1.17±0.27µg.g-1 p<0.05) detected in MasKO mice suggest glomerular hyperfiltration. Histology showed variable degrees of mesagial cells proliferation and segmental glomerulosclerosis, with an increased index of glomerular lesion in MasKO (0.56±0.08 vs. 0.25±0.10 p<0.05). These findings were associated with increased glomerular content of collagens I and IV, fibronectin, Ang II and upregulation of mRNA for AT1 receptor and TGF-beta. TUNEL staining revealed a 2-fold augmentation in fluorescence of apoptotic nuclei from glomerular and tubular cells in MasKO. Our results suggest that Mas receptor may exert protective role on renal fibrosis and apoptosis, possibly counterbalancing Ang II and TGF-beta effects in the kidney.
- © 2011 by American Heart Association, Inc.