[Inhibitory effect of irbesartan on restenosis after balloon angioplasty and mechanism thereof: experiment with rabbits].
OBJECTIVE
To investigate the inhibitory effect of irbesartan on the restenosis after balloon angioplasty and mechanism thereof.


METHODS
Forty-eight Harbin white rabbits underwent balloon angioplasty at the left common carotid artery to establish models of restenosis (RS) and then were randomly divided into 3 groups of 8 rabbits: 7 d, 14 d, and 28 d to be fed with the diet with 35 mg/kg irbesartan till the day when the rabbits were to be killed, each group with 4 controls fed with normal diet At the scheduled days the rabbits were killed and their left common carotid arteries, livers, and kidneys were taken out to undergo morphological examination. The areas of the tunica intima, tunica media, and lumen of the common carotid artery were measured. Immunohistochemistry was used to detect the nuclear factor-kappaB p65 (NF-kappaB p65) and proliferating cell nuclear antigen (PCNA) protein. RT-PCR was used to detect the mRNA expression of inhibitor-kappaB (I-kappaB) and monocyte chemoattractant protein-1 (MCP-1).


RESULTS
No abnormality was found in the specimens of liver and kidney. Measurement showed that the area of tunica intima of the 7 d irbesartan group was 0.34 mm(2) +/- 0.15 mm(2), significantly smaller than that of the controls (1.05 mm(2) +/- 0.38 mm(2), P < 0.05), and the area of arterial lumen of the 28 d group was 4.25 mm(2) +/- 0.29 mm(2), significantly larger than that of the controls (2.56 mm(2) +/- 1.02 mm(2), P < 0.05). Immunohistochemistry showed that the rates of NF-kappaB p65 positive cell and PCNA positive cell of the 7 d irbesartan group were both significantly lower than those of the controls (both P < 0.05). The mRNA expression of I-kappaB in the vascular wall of the 7 d irbesartan group was significantly lower than that of the controls. The mRNA expression levels of MCP-1 at different time points were all significantly lower than those of the corresponding controls (all P < 0.05).


CONCLUSIONS
Irbesartan inhibits the RS after injury of arterial wall by balloon angioplasty via suppressing the activation of NF-kappaB p65 which controls the expression of I-kappaB and MCP-1.
Wang
Jia-hong
JH
Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Huang
Yong-lin
YL
Zhao
Min
M
Cao
Feng-lin
FL
D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics; D023903:Coronary Restenosis / Q000188:drug therapy* / Q000378:metabolism; D015870:Gene Expression; D020672:I-kappa B Proteins / Q000235:genetics; D007150:Immunohistochemistry; D000077405:Irbesartan; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000627:therapeutic use*
D001713:Biphenyl Compounds; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D013777:Tetrazoles; D000077405:Irbesartan