| First Author | Funakoshi H | Year | 2002 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 282 |
| Issue | 6 | Pages | H2159-66 |
| PubMed ID | 12003824 | Mgi Jnum | J:134700 |
| Mgi Id | MGI:3789544 | Doi | 10.1152/ajpheart.00872.2001 |
| Citation | Funakoshi H, et al. (2002) Involvement of inducible nitric oxide synthase in cardiac dysfunction with tumor necrosis factor-alpha. Am J Physiol Heart Circ Physiol 282(6):H2159-66 |
| abstractText | Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor (TNF)-alpha develop dilated cardiomyopathy with myocardial inflammation. The purpose of this study was to investigate the role of nitric oxide (NO) in this mouse model of cardiomyopathy. Female TG and wild-type mice at the age of 10 wk were studied. The expression and activity of inducible NO synthase (iNOS) were significantly increased in the TG myocardium, whereas those of endothelial NOS were not altered. The majority of the iNOS protein was isolated in the interstitial cells. The selective iNOS inhibitor (1S,5S,6R,7R)- 7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0]heptane hydrochloride (ONO-1714) was used to examine the effects of iNOS induction on myocardial contractility. Echocardiography and left ventricular pressure measurements were performed. Both fractional shortening and the maximum rate of rise of left ventricular pressure were significantly suppressed in TG mice. Although ONO-1714 did not change hemodynamic parameters or contractility at baseline, it significantly improved beta-adrenergic inotropic responsiveness in TG mice. These results indicate that induction of iNOS may play an important role in the pathogenesis of cardiac dysfunction in this mouse model of cytokine-induced cardiomyopathy. |
