Abstract P021: The Combined Effects of Elevated Intrarenal Ang Ii and Blood Pressure Causes Greater Renal Injury in the Non-clipped Kidneys in 2k1c Rats

In 2-kidney 1-clip (2K1C) hypertension, intrarenal angiotensin II (Ang II) levels are increased in both kidneys, which are often implicated in the further augmentation of the intrarenal renin-angiotensin system and the development of hypertension and kidney injury. We recently reported that angiotensinogen (AGT) expression and secretion are increased only in the non-clipped kidneys (NCK). These findings provide the basis for the hypothesis that elevated Ang II levels, augmented AGT, and high arteriolar pressure in NCK synergistically cause greater kidney injury. Accordingly, we compared the degrees of kidney injury between clipped kidneys (CK) and NCK using a 2K1C model that maintains normal renal blood flow and GFR in the CK. Left kidneys of male rats were clipped for 21 days. Histological and immunohistological analyses were performed on both the CK and NCK. Twenty glomeruli and 20 microscope fields in the cortex and the medulla were examined for each group. The PAS-positive area in the glomeruli was higher in NCK compared with sham (33.9 ± 0.89 vs. 12.4 ± 0.51%) and CK (vs. 15.1 ± 0.58%). Similarly, the Masson's trichrome-positive area in the medullary region was greater in NCK compared with sham (2.21 ± 0.10 vs. 1.32 ± 0.05%) and CK (vs. 1.67 ± 0.10%), but the changes were not observed in the interstitial tissue of the cortex. Immunoreactivity for CD68, a marker of the macrophage and monocyte levels, was higher in NCK compared with sham (0.72 ± 0.07 vs. 0.36 ± 0.04%), but similar to that in CK. In contrast, accumulation of the immune cells in the glomeruli was greater in NCK compared with sham (8.99 ± 0.69 vs. 3.46 ± 0.46%) and CK (vs. 3.08 ± 0.24%). The proliferating cell nuclear antigen levels, a marker of cell proliferation, were greater in NCK (3.49 ± 0.09 %) but not in the CK. Levels of vimentin, a cell transformation and regeneration marker, were also higher in NCK compared with CK and sham. Increased vascular wall thickness (α-SMA) was observed in both kidneys. These results indicate that pathological factors associated with the high blood pressure are required for the development of renal injury in the 2K1C model including glomerular expansion, medullary fibrosis, immune cell infiltration in glomeruli and cell proliferation/transformation.