IN Vivo Study on Coronary Circulation Under Pharmacologic Inhibition of Endothelium-Derived Relaxing Factor

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(1) Endothelium-derived nitric oxide (EDNO) as a mediator of acetylcholine (ACh)-induced coronary vasodilation in dogs : To investigate the role of EDNO in regulation of the tonus of the coronary artery system in vivo, the effect of N^G-monomethyl-L-arginine (NMA), a specific inhibitor of the synthesis of NO L-arginine, on ACh-induced coronary vasodilation was examined in open-chest, pentobarbital-anesthetized dogs. At baseline, the infusion of ACh and adenosine into the left circumflex artery (LCX) increased the LCX blood flow. Continuous infusion of NMA into LCX significantly attenuated ACh-induced increase in the LCX flow. NMA showed no effect on adenosine-induced increase in the LCX flow. After the NMA infusion was terminated, the effect of ACh partially returned to the baseline level. In other dogs, L-arginine was administered just after the NMA infusion, Which Completely reversed the inhibitory effect of NMA on ACh-induced vasodilation. Thus EDNO is a mediator of ACh-induced vaso … More dilation of the coronary resistance vessels in dogs.(2) Role of endothelium-derived nitric oxide (EDNO) in myocardial reactive hyperemia : In pentobarbital-anesthetized dogs, we investigated the role of the EDNO and adenosine in the regulation of the coronary blood flow during myocardial reactive hyperemia. Repayment of flow debt following 10-, 20-, and 60-second occlusion of the left circumflex artery )LCX) were measured before and after infusion of N^G-monomethyl-L-arginine (NMA), 8-phenyl-theophylline (8-PT) and both NMA and 8-PT in to the LCX. Infusion of NMA significantly reduced repayments of flow debt following 10-, 20-, and 60-second LCX occlusion by means of 30%, 34% and 14%, respectively. Infusion of 8-PT also reduced these repayments of flow debt significantly by means of 31%, 30% and 34%, respectively. Simultaneous infusion of NMA and 8-PT significantly attenuated the peak reactive flow rate and reduced repayment of flow debt following 20-second LCX occlusion by a mean of 57%, and this reduction was significantly greater than each of those by the individual administration of NMA and 8-PT. The suppressive effect of NMA on repayment of flow debt was quickly reversed by the infusion of L-arginine. These results indicate that the myocardial reactive hyperemia is regulated not only by adenosine, but also by the EDNO. Less