Figure 2.

Relative contribution of cellular protection vs. cellular damage of the two main arginine pathways. Panel (I): During ischemia the activation of arginase (Arg) activity reduces the effect of physiological levels of NO on cellular metabolism thereby and reduces otherwise accumulating arginine levels. At this time, inhibition of arginase would be detrimental for the outcome. Panel (II): During early reperfusion, dominance of arginine pathway limits the protective role of NO, specifically on SR-calcium load that triggers fatal arrhythmic events. Moreover, the activated arginase/polyamine pathway potentially augments calcium overload by release polyamines that act on calcium receptors (CaR). Now, the further outcome will benefit from arginase inhibition. Panel (III): At late reperfusion, inflammatory pathways have induced the expression of iNOS that generates detrimental amount of NO that are potentially damaging. In this phase, an inhibition of arginase will be again detrimental, because then more arginine can be converted into NO. Green arrows indicate activation and red arrows indicate inhibition.