Decreased infiltration of macrophages and inhibited activation of nuclear factor-kappa B in blood vessels: a possible mechanism for the anti-atherogenic effects of losartan.
Short-term administration of losartan reduced the aortic surface lesion area and mean intimal thickness. The mechanisms for reducing atherosclerotic progression by losartan may be related to decreased macrophage proliferation and accumulation in the arterial wall, decreased activation of nuclear factor-kappa B and expression of its target gene ICAM-I.


OBJECTIVE
Recent studies suggest that angiotensin II (Ang II) may contribute to the vascular inflammatory response and atherosclerosis. Losartan is a specific AT1 receptor antagonist which can effectively inhibit the effects of Ang II. However, the effects of losartan on atherogenesis have been rarely demonstrated. We designed this study to investigate the effects of short-term administration of losartan on atherosclerotic lesions in the aorta from rabbits fed a cholesterol-enriched diet and the possible mechanisms of its anti-atherogenic effects.


RESULTS
The rabbits were randomly divided into three groups: (a) cholesterol group; (b) losartan-treated group; (c) normal control group. We observed that mean serum lipid levels in the cholesterol group were significantly higher than those in normal control rabbits, while blood pressure between two groups did not change significantly. Treatment with losartan did not affect serum lipid levels or systolic blood pressure but did reduce the aortic surface lesion area and mean intimal thickness. The number of macrophages markedly decreased after administration of losartan. Losartan also attenuated the activation of nuclear factor-kappa B and the expression of its target gene ICAM-I.


CONCLUSIONS
In summary, losartan inhibited atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by losartan may be related to decreased activation of nuclear factor-kappa B.
Xu
Hong-Xin
HX
Department of Cardiology, Renmin Hospital, Wuhan University School of Medicine, People's Republic of China. xu.hongxin@yahoo.com.cn
Li
Jian-Jun
JJ
Li
Geng-Shan
GS
Wang
Jing
J
Li
Ning-Xu
NX
Peng
Jun
J
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002464:Cell Migration Inhibition / Q000187:drug effects*; D004195:Disease Models, Animal; D008055:Lipids / Q000097:blood; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000097:blood; D011817:Rabbits; D011897:Random Allocation
D047228:Angiotensin II Type 1 Receptor Blockers; D008055:Lipids; D016328:NF-kappa B; D019808:Losartan