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1 Journal of Physiology and Pharmacology

1 2010

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Low concentrations of an nitric oxide-donor combined with a liposoluble antioxidant compound enhance protection against reperfusion injury in isolated rat hearts

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Rastalo R. , Cappello S. , Folino A. , Di Stilo A. , Chegaev K. , Tritto I. , Pagliaro P. , Losano G.

nr 1

21-27

Nitric oxide (NO) and reactive oxygen species (ROS) are double-edged swords in reperfused hearts. The effects of a NO-donor and an antioxidant compound against ischemia/reperfusion were studied. The compounds were tested separately, as a mixture and as a new hybrid molecule containing both leads. Isolated rat hearts underwent 30 min global ischemia and 2 hrs reperfusion. Compounds were infused either at 1 or 10 µM concentrations during the first 20 min of reperfusion. Hybrid was also tested in the presence of mitochondrial K+ ATP-sensitive (mKATP) channel blockade by 5-HD (100 µM). Reduction of infarct size and recovery of left ventricular developed pressure during reperfusion were evaluated. When given at 1 µM concentration, hybrid significantly improved all indices of protection; its beneficial effects were abolished by mKATP channel blockade. At the same concentration, mixture and NO-donor alone improved recovery of left ventricular developed pressure but did not reduce infarct size; antioxidant was ineffective. When given at 10 µM concentration, antioxidant and mixture improved all parameters of protection; NO-donor and hybrid were ineffective. Our data suggest that different signaling cascades could be elicited by low and high concentrations of antioxidant compound and/or NO-donor. It is likely that a different NO-induced release of reactive oxygen species via mKATP channel activation may play a pivotal role in affecting infarct size and post-ischemic contractile recovery.