The effects of modulation of the L-arginine-nitric oxide pathway on myocardial stunning following repetitive coronary occlusion in dogs.
In order to determine the role of nitric oxide (NO) in myocardial stunning, the effects of both augmenting and inhibiting NO production on contractile function, following repetitive coronary occlusions, were evaluated in anesthetized dogs. The effect of the experimental protocol on endothelial function was also assessed. The increases in coronary blood flow in response to acetylcholine and nitroglycerin at 30 and 60 min after reperfusion were similar to those before coronary occlusions. Therefore, loss in vasodilator reserve was not observed following the multiple coronary occlusions used in this study. NG-nitro-L-arginine methyl ester (L-NAME) elevated blood pressure slightly, but did not change left ventricular end-diastolic pressure, left ventricular maximum positive dp/dt, and coronary blood flow. Although the degree of systolic bulging and collateral circulation during coronary occlusions was comparable to the control group, contractile function after reperfusion was significantly worse in the presence of L-NAME than in the control. The recovery of contractile function was also considerably delayed with administration of L-arginine. This deleterious effect on contractile function was not observed with its enantiomer D-arginine. Differences in collateral blood flow determined with microspheres and hemodynamic variables did not account for the effects of L-arginine. These results suggest that endogenous NO is important in limiting myocardial stunning following repetitive coronary occlusion. However, NO may be cytotoxic when present in substantial excess.
Morishima
N
N
The First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017682:Myocardial Stunning / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester