title: Nitric oxide participates in the negative inotropic effect of interferon-alpha in rat cardiac muscle.
abstract: In clinical practice, interferon-alpha (IFN-alpha) has been widely used as an antiviral, antitumor and immunomodulatory agent. However, its intravenous administration at large doses is associated with significant cardiovascular side-effects such as congestive heart failure and myocardial infarction. But the direct cardiovascular effects of IFN-alpha and the underlying mechanisms are not clear. In this study, we investigated the effects of IFN-alpha on contractility in Langendorff perfused rat hearts and isolated rat papillary muscles. The results showed that IFN-alpha induced a concentration-dependent negative inotropic effect in the isolated heart and papillary muscle. Pretreatment with L-NAME, a nitric oxide synthase inhibitor, attenuated this inotropic effect. Furthermore, in isolated papillary muscles IFN-alpha decreased the responsiveness to the beta-agonist isoproterenol, which was also attenuated by pretreatment with L-NAME. In conclusion, these results show that IFN-alpha induced a negative inotropic effect in normal and beta-adrenergic activated cardiac muscle at least partly via nitric oxide (NO).
authors.affiliation: Dept. of Physiol., Zhejiang Univ., Hangzhou.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: He
authors.forename: Iain C
authors.initials: IC
authors.lastname: Bruce
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia