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 N(G)-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-mu-mol/min, for 20 min) reduced repayments of flow debt after 10-, 20-, and 60-s LCX occlusion by 30 +/- 4 (P < 0.01), 34 +/- 3 (P < 0.01), and 14 +/- 3% (P < 0.01), respectively. Infusion of 8-PT (0.75-mu-mol/min for 15 min) also reduced these repayments of flow debt by 31 +/- 7 (P < 0.01), 30 +/- 7 (P < 0.01), and 34 +/- 6% (P < 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 < 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 < 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). These results indicate that the myocardial reactive hyperemia is regulated not only by adenosine but also by the endothelium-derived nitric oxide.