L-arginine enhances functional recovery and Ca²⁺-dependent nitric oxide synthase activity after ischemia and reperfusion in the rat heart

The effects of L-arginine on ischemia/reperfusion-induced myocardial dysfunction as well as the tissue activity of nitric oxide synthase (NOS) were investigated in rat isolated Langendorff-perfused hearts. Hearts were subjected to nonischemic perfusion or 30 min of global ischemia followed by 30 min of reperfusion. The hearts subjected to ischemia/reperfusion received either vehicle, L-arginine (1 mM), D-arginine (1 mM), the NOS inhibitor N(G)-nitro-L-arginine (L-NNA, 1 mM), or L-arginine (1 mM) plus L-NNA (1 mM) at the beginning of ischemia. L-Arginine but not D-arginine significantly enhanced the recoveries of left ventricular double product and coronary flow compared with the vehicle group. There was a substantial activity of Ca²⁺- dependent NOS but no significant Ca²⁺-independent NOS activity in the hearts undergoing 60 min of nonischemic perfusion. After ischemia/reperfusion, Ca²⁺dependent NOS activity significantly decreased (by >90%) in comparison with that of nonischemic hearts. L-Arginine increased the Ca²⁺-dependent NOS activity compared with the vehicle group to a level that was similar to that observed in nonischemic hearts. There was no difference in Ca²⁺-dependent NOS activity between vehicle- and D- arginine-treated groups. Administration of L-NNA abolished the beneficial effects of L-arginine on functional recovery and on Ca²⁺-dependent NOS activity. There were no significant Ca²⁺-independent NOS activities in any of the ischemic groups. These results suggest that myocardial ischemia/reperfusion reduces Ca²⁺-dependent NOS activity in the heart. Administration of L-arginine enhances myocardial function and preserves Ca²⁺-dependent NOS activity after ischemia/reperfusion through a pathway involving NOS activity.