Role of adenosine in regulation of coronary flow in dogs with inhibited synthesis of endothelium-derived nitric oxide.
Endothelium-derived nitric oxide (NO) regulates coronary blood flow, but it is unclear how NO synthesis inhibition affects myocardial metabolism. In pentobarbital sodium-anesthetized dogs, myocardial oxygen metabolism, adenosine release, lactate extraction rate (LER), and systolic ventricular wall thickening (SWT) at baseline and during atrial pacing were estimated before and after intracoronary NG-nitro-L-arginine methyl ester (L-NAME) infusion. Coronary blood flow and PO2 in the anterior interventricular vein at baseline were both significantly decreased by L-NAME (3 x 10(-4) M in the coronary blood). Coronary flow was increased during pacing, which was not affected by L-NAME. Myocardial adenosine release remained unchanged during pacing before L-NAME, but it was significantly increased after L-NAME infusion. Neither LER nor SWT changed during pacing performed before and after L-NAME. The experiment was also performed in dogs pretreated with 8-phenyltheophyl-line. After L-NAME, pacing-induced increase in coronary flow was suppressed, and both LER and SWT were significantly decreased during pacing. In conclusion, when NO synthesis is inhibited, adenosine release is increased in response to the increase in myocardial oxygen demand. With this compensatory adenosine release, coronary flow is increased and ventricular function is unaffected.
Matsunaga
T
T
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Okumura
K
K
Tsunoda
R
R
Tayama
S
S
Tabuchi
T
T
Yasue
H
H
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D016275:Atrial Function; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism*; D005740:Gases / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007269:Injections, Intra-Arterial; D019344:Lactic Acid / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D005740:Gases; D009569:Nitric Oxide; D019344:Lactic Acid; D013806:Theophylline; C028322:8-phenyltheophylline; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester