RESUMO
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.