[Renal protective effect of angiotensin II receptor antagonist on growth hormone-treated nephrotic 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.


CONCLUSIONS
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.
Li
Shuang
S
Department of Nephrology, Suzhou Children's Hospital, Suzhou University, Suzhou 215000 China.
Cao
Bin
B
Feng
Qi-hua
QH
Li
Xiao-zhong
XZ
D000804:Angiotensin II / Q000032:analysis; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D024141:Collagen Type IV / Q000032:analysis; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005353:Fibronectins / Q000032:analysis; D013006:Growth Hormone / Q000494:pharmacology*; D007150:Immunohistochemistry; D000077405:Irbesartan; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy*; D007678:Kidney Glomerulus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D011507:Proteinuria / Q000652:urine; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000032:analysis; D014280:Triglycerides / Q000097:blood
D057911:Angiotensin Receptor Antagonists; D000903:Antibiotics, Antineoplastic; D001713:Biphenyl Compounds; D024141:Collagen Type IV; D005353:Fibronectins; D012709:Serum Albumin; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D000804:Angiotensin II; D004317:Doxorubicin; D013006:Growth Hormone; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A; D000077405:Irbesartan