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Angiotensin II induced increase in eNos is mediated through TNF‐a
Author(s) -
Hartfield Julie N,
Haque Masudul,
Majid Dewan S.A.,
Francis Joseph
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a722
Subject(s) - enos , medicine , endocrinology , nox4 , angiotensin ii , tumor necrosis factor alpha , ventricle , pathogenesis , renin–angiotensin system , nadph oxidase , chemistry , oxidative stress , nitric oxide synthase , nitric oxide , blood pressure
Angiotensin II (ANG II) and Tumor necrosis factor‐α (TNF‐α) play an important role in the pathogenesis of cardiovascular disease. Recently we showed that NADPH oxidase (Nox) subunit gp91 phox and its homologues Nox1 and Nox4 are increased in the left ventricle (LV) of ANG II treated mice, and these increases are mediated through TNF‐α. In this study, we examined whether ANG II‐induced increase in eNOS expression in the LV is mediated through TNF‐α. Method ANGII (1μg/kg/min) or VEH was infused using osmotic minipumps in wildtype (n=9) and TNF‐α (−/−) mice (n=8) for 14 days. In one group of ANGII infused TNF‐α (−/−) mice (n=8), was treated with recombinant TNF‐α (10ng/day) for 14 days. On day 14, LV function was assessed using echocardiography. Subsequently, myocardial eNOS expression was measured by real‐time PCR. Results ANG II induced a significant increase in eNOS mRNA expression in the LV of wildtype mice but not in the TNF‐α (−/−) mice. When TNF‐α was replaced in a TNF‐α (−/−) mouse, eNOS mRNA expression was increased due to ANG II treatment. LV function and blood pressure response are being investigated. Conclusions 1) These results indicate that TNF‐α.plays a mediatory role in ANG II‐induced increases in eNOS activity at least in the myocardium. 2) Collectively these data suggest an important modulatory role of cytokines in the nitrosative and oxidative stress mechanisms induced by ANGII.