Effects of angiotensin-II receptor blockers on experimental autoimmune myocarditis.
BACKGROUND
The effects of angiotensin-II type 1 receptor blockers (ARBs) on the treatment of hypertension, heart failure, and other cardiovascular diseases have been confirmed extensively. However, recent studies have emphasized the nonhemodynamic effects of these drugs. The purpose of this study was to investigate the effects of ARBs on the development of experimental autoimmune myocarditis (EAM), and to clarify the mechanisms involved.


METHODS
EAM model was induced in Lewis rats by injection of porcine cardiac myosin subcutaneously. We administered valsartan (a new ARB) to rats with EAM and measured blood pressure regularly. Echocardiography was performed to examine the cardiac function and heart structure of the rats. The severity of myocarditis was detected by histopathological evaluation. We evaluated antigen-specific T-cell proliferation responses to cardiac myosin by the lymphocyte proliferation assay and measured serum levels of Th1 and Th2 cytokines by enzyme-linked immunosorbent assay.


RESULTS
There was no significant difference in the blood pressure (BP) level between the groups and cardiac function of valsartan-treated rats was significantly improved compared with untreated rats. Valsartan markedly reduced the severity of myocardial lesions and suppressed lymphocyte proliferation in rats immunized with myosin. After drug administration, Th1 cytokines (IFN-gamma and IL-2) were significantly down-regulated, while Th2 cytokines (IL-4 and IL-10) were detected to undergo up-regulation.


CONCLUSIONS
The results suggest that valsartan can ameliorate EAM independent of BP-lowering effects. Some of the beneficial effects of ARBs may be due to their immunomodulatory reactions in the modification of helper T-cell balance.
Liu
Xuefei
X
Department of Cardiology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, 250021, PR China.
Zhu
Xinglei
X
Wang
Aiying
A
Fan
Hui
H
Yuan
Haitao
H
D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013777:Tetrazoles / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D016207:Cytokines; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine