Effect of chronic and progressive aortic constriction on renal function and structure in rats

Abstract

The purpose of this study was to evaluate the functional and structural renal damage observed in aortic-constricted hypertensive rats and to identify their possible relationship with transforming growth factor β (TGF-β) expression. Progressive renovascular hypertension was induced by progressive aortic constriction between the two renal arteries. Three months after constriction, the glomerular filtration rate (GFR), effective renal blood flow (ERBF), perfusion pressure (PP), urinary protein excretion (UPE) and urinary electrolyte excretion (UNaV and UKV) in the kidney above (right kidney, RK) and below the ligature (left kidney, LK) were measured. The cross-sectional corpuscular, capillary tuft and mesangial matrix area and tubulo-interstitial fibrosis were measured in tissue sections stained with Syrius Red using a computer-assisted image analysis system. TGF-β was detected by immunohistochemistry. The functional parameters were similar in the two kidneys of aortic-constricted hypertensive rats (GFR-RK, 1.33 ± 0.08 vs. LK, 1.18 ± 0.08 mL/min; ERBF-RK, 9.23 ± 1.32 vs. LK, 8.18 ± 0.91 mL/min; RVR-RK, 28.3 ± 3.9 vs. LK, 21.7 ± 3.2 mmHg·min/mL). The RK was subject to a higher PP than the LK (176 ± 7 vs. 128 ± 5 mmHg, P < 0.05). UPE, UNaV, and UKV were greater in the RK than in the LK (UPE-RK, 512 ± 61 vs. LK, 361 ± 38 µg/30 min, P < 0.05; UNaV-RK, 0.056 ± 0.012 vs. LK, 0.022 ± 0.006 mEq/30 min, P < 0.05; UKV-RK, 0.042 ± 0.006 vs. LK, 0.029 ± 0.003 mEq/30 min, P < 0.05). Morphometric analysis revealed that the RK capillary tuft area and mesangial matrix area were higher than those in the LK. The LK had a higher degree of interstitial fibrosis than the RK. No significant differences in TGF-β immunostaining were observed between the RK and the LK. In conclusion, the RK (subjected to hypertension) of aortic-constricted hypertensive animals developed glomerular fibrosis, only in the outer glomeruli whereas the LK developed mild interstitial fibrosis. Neither glomerular nor interstitial fibrosis seem to be responsible for the proteinuria observed in both kidneys.Key words: renovascular hypertension, renal fibrosis, rats, TGF-β.