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[Renal protective effect of angiotensin II receptor antagonist on growth hormone-treated nephrotic rats]
Shuang Li1, Bin Cao, Qi-hua Feng
1Department of Nephrology, Suzhou Children's Hospital, Suzhou University, Suzhou 215000 China.
Insights
Growth hormone (GH) worsens kidney damage in rats with adriamycin-induced nephropathy (AN) by activating the renin-angiotensin system (RAS). Irbesartan, an angiotensin II receptor antagonist, offers renoprotection in GH-treated AN rats.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Children with nephrotic syndrome often experience growth retardation.
- Growth hormone (GH) can stimulate growth but may exacerbate glomerulosclerosis.
- Adriamycin-induced nephropathy (AN) in rats serves as a model for kidney disease.
Purpose of the Study:
- To investigate the effect of GH on kidneys in AN rats.
- To elucidate the mechanism by which GH affects AN.
- To evaluate the renoprotective effect of irbesartan in GH-treated AN rats.
Main Methods:
- Rats were divided into four groups: control, AN, GH-treated AN, and GH plus irbesartan-treated AN.
- Evaluated urinary protein, blood pressure, serum creatinine, BUN, albumin, lipids, ACE activity, and kidney Angiotensin II (AngII) concentration.
- Assessed renal pathology and immunohistochemically examined TGF-β1, collagen IV, and fibronectin expression.
Main Results:
- GH significantly increased glomerular sclerosis, urinary protein, hyperlipidemia, hypoalbuminemia, and azotemia in AN rats.
- GH treatment elevated kidney ACE activity and AngII concentration, alongside increased TGF-β1, collagen IV, and fibronectin expression.
- Irbesartan treatment reduced glomerular sclerosis and TGF-β1, collagen IV, and fibronectin expression in GH-treated AN rats.
Conclusions:
- GH exacerbates adriamycin-induced nephropathy in rats, partly by activating the renal renin-angiotensin system (RAS) and the AngII-TGF-β1-extracellular matrix axis.
- Angiotensin II receptor antagonist irbesartan demonstrates renoprotective effects in GH-treated AN rats.
Objective:
Children with nephrotic syndrome are always associated with retardation of growth. Growth hormone (GH) administration to these children can stimulate their growth, but it plays an important role in glomerulosclerosis. Thus these children would take a risk to use it to improve their growth. This study was designed to investigate the effect of GH on the kidney of rats with adriamycin-induced nephropathy (AN) and its mechanism, and to observe the renoprotective effect of angiotensin II (AngII) receptor antagonist, irbesartan, in GH-treated AN rats.
Methods:
Rats were divided into the following groups: normal control rats, AN rats, GH-treated AN rats and GH plus irbesartan-treated AN rats. There were 8 developing male SD rats (120-130 g) in each group. Urinary protein was measured at weeks 3, 6 and 9. Blood pressure, serum creatinine, BUN, albumin, cholesterol, triglyceride, as well as ACE activity and AngII concentration of the kidney were detected at the end of the study. Renal pathological changes were evaluated also. Immunohistochemistry was used to examine the protein expressions of TGF beta(1), collagen IV and fibronectin in glomeruli.
Results:
Glomerular sclerosis score of GH-treated AN rats (49.4 +/- 9.8) was significantly higher than that of AN rats (12.8 +/- 5.5, P < 0.01), and this score of GH-treated AN rats plus irbesartan (26.2 +/- 7.5) was significantly lower than the score of GH-treated AN rats (P < 0.01). The changes of urinary protein, hyperlipidemia and hypoalbuminemia in rats of each group consisted with the degree of glomerular injury in rats of each group. There was azotemia in GH-treated AN rats, but rats in the other groups did not have azotemia. ACE activity of kidney was significantly (P < 0.01) increased in GH-treated AN rats [(28.1 +/- 4.1) U/mg pro] and GH-treated AN rats plus irbesartan [(27.6 +/- 3.4) U/mg pro] compared with that in AN rats [(14.6 +/- 4.4) U/mg pro]. AngII concentrations in the kidney of GH-treated AN rats [(17.8 +/- 3.3) pg/mg pro] and GH-treated AN rats plus irbesartan [(27.3 +/- 5.1) pg/mg pro] were significantly higher than that in AN rats [(8.3 +/- 1.9) pg/mg pro] (P < 0.01). The protein expressions of TGF-beta(1), collagen IV and fibronectin in GH-treated AN rats were the most distinct in all groups. These expressions were significantly (P < 0.05) reduced in GH-treated AN rats plus irbesartan.
Conclusion:
GH is able to exacerbate adriamycin-induced nephropathy in rats, which was partly through activating renal tissue RAS and initiating the function of the AngII-TGF beta(1)-ECM axis. Angiotensin II receptor antagonist, irbesartan, has some renal protective effects on AN rats treated with GH.
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