Regional coronary haemodynamic effects of two inhibitors of nitric oxide synthesis in anaesthetized, open-chest dogs.
1. The role of endothelial nitric oxide synthesis from L-arginine in the regulation of coronary vascular tone and myocardial tissue perfusion was evaluated in anaesthetized, open-chest dogs. Coronary blood flow was measured with an electromagnetic flow probe placed around the left circumflex coronary artery. Coronary vascular resistance was calculated from mean arterial blood pressure and mean coronary blood flow, whereas regional myocardial tissue flow was determined by use of the radioactive microspheres technique. 2. NG-monomethyl L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), administered directly into the left circumflex artery, induced a small increase in arterial blood pressure and an increase in coronary vascular resistance. However, myocardial tissue perfusion, assessed by the microspheres technique (whether subendocardial, subepicardial, or transmural), was unaffected by L-NMMA or L-NAME. 3. Acetylcholine, administered intracoronarily, induced an increase in left circumflex coronary blood flow and a decrease in coronary vascular resistance, without affecting systemic haemodynamics. This coronary vasodilator effect of acetylcholine was markedly inhibited by L-NMMA and L-NAME, the latter being a more potent antagonist than the former. 4. These results indicate that the endothelial L-arginine pathway is largely responsible for the coronary vasodilator effect of acetylcholine. However, although basal release of nitric oxide from L-arginine apparently contributes to the regulation of resting coronary vascular tone, blockade of this pathway does not affect myocardial tissue perfusion, possibly because of compensatory mechanisms occurring at the level of small arterioles and/or capillaries.
Richard
V
V
Laboratoire de Pharmacologie, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France.
Berdeaux
A
A
la Rochelle
C D
CD
Giudicelli
J F
JF
D000109:Acetylcholine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008863:Microspheres; D009129:Muscle Tonus / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester