[Involvement of nitric oxide in negative inotropic effect of interferon-alpha in rat cardiac muscle].
To investigate the effects and underlying mechanisms of interferon-alpha (IFN-alpha) on the isolated Langendorff perfused rat hearts and the isolated papillary muscles.



The left ventricular developed pressure (LVDP), maximal rise/fall rate of left ventricular pressure (+/-dP/dt(max)), left ventricular end-diastolic pressure (LVEDP), heart rate (HR) and coronary flow (CF) were recorded in isolated Langendorff perfused rat hearts. The average contractile force was measured in the isolated papillary muscles of rat right ventricle.



IFN-alpha (10 - 10,000 U/ml) induced a concentration-dependent decrease of LVDP and +/-dP/dt(max), and increase of LVEDP and CF in the isolated perfused rat heart (P < 0.05), and decrease of the average contractile force of the papillary muscle (P <0.05). Pretreatment with L-NAME (10(-4) mol/L), an inhibitor of nitric oxide synthase, attenuated the effect of IFN-alpha in the isolated rat hearts and the isolated papillary muscles (P <0.05). Isoproterenol (ISO, 10(-9) - 10(-6)mol/L) increased the contractile force of the rat papillary muscles in a concentration-dependent manner. Perfusion for 10 min with IFN-alpha at 1,000 U/ml attenuated the enhancing effect of ISO. Pretreatment with L-NAME reduced the effects of IFN-alpha on the isolated papillary muscles.



IFN-alpha may induce a negative inotropic effect in normal and beta-adrenergic activated cardiac muscles and this effect at least partly be mediated by nitric oxide.
Yao
Hui
H
Hangzhou Normal College School of Basic Medicine, Hangzhou 310012, China.
Xia
Man-Li
ML
He
Xiao-Hong
XH
Xia
Qiang
Q
D000818:Animals; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D016898:Interferon-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester