Korean J Nephrol.  2001 May;20(3):413-426.

The Role of Renin-Angiotensin System in Progressive Renal Injury

• Lee KW
• Song JH
• Kang MK
• Hwang PJ
• Kim JH
• Na KR
• Suh KS
• Park JK
• Shin YT

Abstract

Angiotensin II(A II) -a main effector molecule of renin-angiotensin system(RAS) has been known to increase blood pressure and glomerular capillary pressure, and filtration fraction which may be involved in the progressive renal injury process. The action of A II takes place mainly through AT1 receptor. RAS can be blocked by angiotensin converting enzyme inhibitor(ACEI) and recently developed A II AT1 receptor antagonist(AT1 RA). ACEI also activate kinin system, simultaneously. However, AT1 RA does not affect kinin system. The renoprotective mechanism of ACEI may be related with activation of kinin system. In order to evaluate the renoprotective mechanism of long-term ACEI(enalapril, 100mg/L in drinking water for 12 weeks) or AT1 RA treatment(losartan 300mg/L in drinking water for 12 weeks), and its effect on the cytokines and growth factor expressions of renal cortical tissue by compatitive RT-PCR, 46 5/6 nephrectomized(5/6 NPX) rats and 8 sham operated rats were included in this study. Five sixth NPX rats showed marked hypertensin, significant proteinuria and glomerulosclerosis(mean 30.5%) in 12 weeks after surgery. However, enelapril or losartan treated rats revealed significantly lower 24 hour urinary protein excretion(UProtV), systolic blood pressure(SBP), and glomerulosclerosis than those of control 5/6 NPX rats. Plasma renin activity and angiotensin II levels of 5/6 NPX untreated control rats were not significantly increased compared to sham operated rats in 12 week after surgery. Renal cortical renin gene expression of untreated 5/6 NPX rats was significantly suppressed compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly increased renin gene expression compared to untreated 5/6 NPX rats. Renal cortical gene expressions of TGF-beta, TNF-alpha, MCP-1, IL-6, osteopontin, and endothelin-1 were significantly increased in 5/6 NPX untreated control rats compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly less level of renal TGF-beta gene expression compared to 5/6 NPX control rats. The magnitude of SBP and UProtV were significantly positively correlated with the degree of glomeruloslerosis(p<0.001, p<0.001). With the above result, we speculate that because ACEI or AT1 RA showed similar renoprotective effect in 5/6 NPX rats, at least in part, local activation of RAS plays an important role in the progressive renal injury process of this model.

Keyword

Renin-angiotensin system; Angiotensin converting enzyme inhibitor; Angiotensin II AT1 receptor antagonist; 5/6 nephrectomy; Cytokine; Renal injury

MeSH Terms

Angiotensin Amide
Angiotensin II
Angiotensins
Animals
Blood Pressure
Capillaries
Cytokines
Drinking Water
Enalapril
Endothelin-1
Filtration
Gene Expression
Interleukin-6
Losartan
Osteopontin
Peptidyl-Dipeptidase A
Plasma
Proteinuria
Rats
Renin
Renin-Angiotensin System*
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha
Angiotensin Amide
Angiotensin II
Angiotensins
Cytokines
Drinking Water
Enalapril
Endothelin-1
Interleukin-6
Losartan
Osteopontin
Peptidyl-Dipeptidase A
Renin
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha