L-arginine enhances functional recovery and Ca(2+)-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 NG-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 Ca(2+)-dependent NOS but no significant Ca(2+)-independent NOS activity in the hearts undergoing 60 min of nonischemic perfusion. After ischemia/reperfusion, Ca(2+)-dependent NOS activity significantly decreased (by > 90%) in comparison with that of nonischemic hearts. L-Arginine increased the Ca(2+)-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 Ca(2+)-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 Ca(2+)-dependent NOS activity. There were no significant Ca(2+)-independent NOS activities in any of the ischemic groups. These results suggest that myocardial ischemia/reperfusion reduces Ca(2+)-dependent NOS activity in the heart. Administration of L-arginine enhances myocardial function and preserves Ca(2+)-dependent NOS activity after ischemia/reperfusion through a pathway involving NOS activity.
Wang
Q D
QD
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
Morcos
E
E
Wiklund
P
P
Pernow
J
J
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D002118:Calcium