Role of endothelium-derived nitric oxide in myocardial reactive hyperemia.
In pentobarbital sodium-anesthetized dogs we investigated the role of the endothelium-derived nitric oxide and adenosine in the regulation of the coronary blood flow during myocardial reactive hyperemia. Repayments of flow debt after 10-, 20- and 60-s occlusion of the left circumflex coronary artery (LCX) were measured before and after infusion of NG-monomethyl-L-arginine (L-NMMA; n = 15), 8-phenyltheophylline (8-PT; n = 5), and both L-NMMA and 8-PT (n = 5) into the LCX. Infusion of L-NMMA (2 mumol/min, for 20 min) reduced repayments of flow debt after 10-, 20-, and 60-s LCX occlusion by 30 +/- 4 (P less than 0.01), 34 +/- 3 (P less than 0.01), and 14 +/- 3% (P less than 0.01), respectively. Infusion of 8-PT (0.75 mumol/min for 15 min) also reduced these repayments of flow debt by 31 +/- 7 (P less than 0.01), 30 +/- 7 (P less than 0.01), and 34 +/- 6% (P less than 0.01), respectively. Simultaneous infusion of L-NMMA and 8-PT significantly attenuated the peak reactive flow rate and reduced repayment of flow debt after 20-s LCX occlusion by 57 +/- 1% (P less than 0.001), and this reduction in repayment of flow debt was significantly greater than each of those by the individual administration of L-NMMA and 8-PT (both P less than 0.01). The suppressive effect of L-NMMA on repayment of flow debt after 20-s LCX occlusion was quickly reversed by the infusion of L-arginine (3 mg/min for 10 min; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Yamabe
H
H
Division of Cardiology, Kumamoto University Medical School, Japan.
Okumura
K
K
Ishizaka
H
H
Tsuchiya
T
T
Yasue
H
H
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D009202:Cardiomyopathies / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism*; D006940:Hyperemia / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D014677:Pharmaceutical Vehicles; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D019323:omega-N-Methylarginine
D004338:Drug Combinations; D014677:Pharmaceutical Vehicles; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine