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Role of nitric oxide in iron-induced toxicity in rat hearts

Chen Yingying, Xia Qiang, Cao Chunmei, Ye Zhiguo, Shen Yueliang, Wang Linlin

Department of Physiology, Zhejiang University School of Medicine,Hangzhou(310031)

Abstract

The aim of the present study was to explore the effect of nitric oxide (NO) on iron-induced toxicity in rat hearts. Langendorff perfused rat heart and enzymatically isolated cardiomyocytes were used. It was shown that lipophilic Fe-HQ reduced the contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte, while the left ventricular developed pressure (LVDP), ±dp/dt_(max), heart rate and coronary flow showed biphasic alterations, which increased in the first 2 min and then was followed by a decline in isolated perfused rat heart; the contents of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the malondialdehyde (MDA) in the myocardium were increased. L-arginine (L-Arg), an NO precursor, reduced the contractile amplitude and end-diastolic cell length in the cardiomyocyte; but reversibly increased LVDP, ±dp/dt_(max), and coronary flow in isolated perfused rat heart. Pretreatment with L-Arg aggravated the Fe-HQ-induced decrease in contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte; LVDP, ±dp/dt_(max), heart rate and coronary flow were significantly reduced in the perfused heart, and the levels of LDH and CK increased in the coronary effluent. In contrast, the NOS inhibitor N_ω-nitro-L-arginine methyl ester (L-NAME) blocked the Fe-HQ induced change in contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte; it inhibited the decrease in LVDP, LVEDP and ±dp/dt_(max), and reduced the LDH and CK. Removing endothelial cells in coronary vessels attenuated the increase in LVDP and ±dp/dt_(max) at the beginning of Fe-HQ perfusion. It is suggested that L-Arg aggravates the iron-induced cardiac dysfunction, No can mediate the iron-induced toxicity in heart, and endothelial cells in coronary vessels play an important role in the early stage of the effect of iron.

Key words: Iron;Heart;Nitric oxide;L-Arginine;NG-nitroarginine methyl ester

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Citing This Article：

Chen Yingying, Xia Qiang, Cao Chunmei, Ye Zhiguo, Shen Yueliang, Wang Linlin. Role of nitric oxide in iron-induced toxicity in rat hearts. Acta Physiol Sin 2002; 54 (4): (in Chinese with English abstract).