Effects of angiotensin II receptor blockade on hepatic fibrosis in rats.
OBJECTIVE
To investigate the effects of angiotensin II type 1 receptor blockade, losartan, on serum levels of components of extracellular matrix in experimental fibrotic rats.


METHODS
Fifty male Spague-Dawley rats were separated into five groups (control, model, and 3 treatment groups). Excepting rats in control group, all rats were given subcutaneous injection of 40% carbon tetrachloride (once every 3 days for 6 weeks). Rats in 3 treatment groups were also given losartan of 10mg/kg, 5mg/kg, 2.5mg/kg daily for 6 weeks via gastrogavage, respectively. At the end of sixth week, all rats were sacrificed. Radioimmunoassay was performed to determine the serum levels of hyaluronic acid (HA), Laminin (LN), procollagen type III (PCIII) and collagen type IV. Van Giesion collagen staining was used to evaluate the extracellular matrix of the liver tissue.


RESULTS
Compared with model group, losartan significantly reduced the serum levels of HA [from (911.66 +/- 345.49)microg/L to (425.05 +/- 115.80)microg/L], LN [from (209.87 +/- 91.57)microg/L to (83.56 +/- 22.12)microg/L, PCIII [from (31.82 +/- 6.90)microg/L to (22.78 +/- 8.38)microg/L] and collagen IV [from (54.09 +/- 19.81)microg/L to (30.51 +/- 12.39)microg/L] (P<0.05) and greatly attenuated the degree of liver fibrosis (P<0.05).


CONCLUSIONS
Losartan can markedly reduce the serum levels of LN, HA, PCIII and collagen type IV of fibrotic rats induced by CCl(4) and greatly attenuate the degree of liver fibrosis.
Wei
H
H
Department of Gastroenterology, Xinhua Hospital, Shanghai Second Medical University, Shanghai 200092, China.
Li
D
D
Lu
H
H
Zhan
Y
Y
Wang
Z
Z
Huang
X
X
Pan
Q
Q
Xu
Q
Q
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D003094:Collagen / Q000097:blood; D006820:Hyaluronic Acid / Q000097:blood; D007797:Laminin / Q000097:blood; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
D057911:Angiotensin Receptor Antagonists; D007797:Laminin; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D006820:Hyaluronic Acid; D003094:Collagen; D019808:Losartan