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 d ysfunction as well as the tissue activity of nitric oxide synthase (NO S) were investigated in rat isolated Langendorff-perfused hearts. Hear ts were subjected to nonischemic perfusion or 30 min of global ischemi a 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-argini ne (1 mM) plus L-NNA (1 mM) at the beginning of ischemia. L-Arginine b ut not D-arginine significantly enhanced the recoveries of left ventri cular double product and coronary flow compared with the vehicle group . There was a substantial activity of Ca2+-dependent NOS but no signif icant 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 activ ity compared with the vehicle group to a level that was similar to tha t observed in nonischemic hearts. There was no difference in Ca2+-depe ndent NOS activity between vehicle- and D-arginine-treated groups. Adm inistration 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 gr oups. These results suggest that myocardial ischemia/reperfusion reduc es Ca2+-dependent NOS activity in the heart. Administration of L-argin ine enhances myocardial function and preserves Ca2+-dependent NOS acti vity after ischemia/reperfusion through a pathway involving NOS activi ty.