[Role of nitric oxide in iron-induced toxicity in rat hearts].
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(omega)-nitro-L-arginine methyl ester (L-NAME) blocked the Fe-HQ induced change in contractile amplitude, velocity and end-diastolic cell length in the cardio- myocyte; 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.
Ying-Ying
Chen
C
Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310031.
Qiang
Xia
X
Chun-Mei
Cao
C
Zhi-Guo
Ye
Y
Yue-Liang
Shen
S
Lin-Lin
Wang
W
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology; D003402:Creatine Kinase / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007501:Iron / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats
D009569:Nitric Oxide; D008315:Malondialdehyde; D001120:Arginine; D007501:Iron; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D019331:NG-Nitroarginine Methyl Ester