Endothelium-derived nitric oxide as a mediator of acetylcholine-induced coronary vasodilation in dogs.
To investigate the role of endothelium-derived nitric oxide (NO) in regulation of the tonus of the coronary artery system in vivo, the effect of NG-mono-methyl-L-arginine (L-NMMA), a specific inhibitor of the synthesis of NO from L-arginine, on acetylcholine (ACh)-induced coronary vasodilation was examined in open-chest, anesthetized dogs. At baseline, the infusion of ACh and adenosine into the left circumflex coronary artery (LCX) increased the LCX blood flow. Continuous infusion of L-NMMA (2 mumol/min, for 20 min) into LCX significantly attenuated ACh-induced increase in the LCX flow: percentage increases in the LCX flow by ACh (10 and 100 ng/kg) before L-NMMA were 42.0 +/- 8.7 and 137.3 +/- 12.5%, respectively, whereas those after L-NMMA were 14.0 +/- 4.9 (p less than 0.02) and 88.9 +/- 10.9% (p less than 0.005), respectively. L-NMMA showed no effect on adenosine-induced increase in the LCX flow. After the L-NMMA infusion was terminated, the effect of ACh partially returned to the baseline level. In other dogs, L-arginine (3 mg/min, for 20 min) was administered just after the L-NMMA infusion, which completely reversed the inhibitory effect of L-NMMA on ACh-induced vasodilation. Endothelium-derived NO is a mediator of ACh-induced vasodilation of the coronary resistance vessels in dogs.
Ishizaka
H
H
Division of Cardiology, Kumamoto University Medical School, Japan.
Okumura
K
K
Yamabe
H
H
Tsuchiya
T
T
Yasue
H
H
D000109:Acetylcholine / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000241:Adenosine; D000109:Acetylcholine