A Study on the Regulation of CoronaryBlood Flow in the condition of Inhabited Synthesis of Endothelium-Derived Nitric Oxide

为了阐明内皮源性一氧化氮(EDNO)在冠脉血流调节中的作用，我们在麻醉犬身上进行了体内研究。结果表明，EDNO在基础冠脉血流中起调节作用(Arch int Pharmacdyn 1994；327：251-265)，心肌反应性充血(RH)不仅由腺苷介导，而且由EDNO介导(Am J Physiol1992；263：H4-H14)。最近，我们研究了锰超氧化物歧化酶对麻醉犬RH的影响，发现缺血60s和再灌流时产生的超氧阴离子自由基通过灭活EDNO而减弱心肌RH(心血管Res 1996；31：537-545)。还表明，当NO的合成被L-精氨酸类似物LNAME抑制时，腺苷的释放随着心肌需氧量的增加而增加，冠脉流量增加，而心功能不受影响(Am J Physiol 1996；270：H427-H434)。口服L-NAME 4周，慢性抑制NO生成，可钝化冠脉反应性充血，但不显著损害冠脉血流对心房起搏所产生的心肌耗氧量增加的反应。因此，腺苷可能也在慢性NO合成抑制模型中发挥作用(Jpn CRIC J，1998，在PRESS)。

To clarify the role of endothelium-derived nitric oxide (EDNO) on the regulation of coronary blood flow, we performed in-vivo studies in anesthetized dogs. It was revealed that EDNO plays a role in the regulation of the basal coronary blood flow (Arch int Pharmacodyn 1994 ; 327 : 251-265), and that myocardial reactive hyperemia (RH) is mediated not only by adenosine but by EDNO (Am J Physiol 1992 ; 263 : H4-H14). Recently, we examined the effect of manganese (Mn)-superoxide dismutase (SOD) on RH in anesthetized dogs, and revealed superoxide redicals generated during ischemia for 60s and reperfusion attenuates myocardial RH through inactivation of EDNO (Cardiovascular Res 1996 ; 31 : 537-545).It was also shown that Mn-SOD shows more beneficial effects on myocardial RH than Cu, Zn-SOD.We also showed that when NO synthesis is inhibited by L-arginine analogue, LNAME,adenosine release is increased in response to the myocardial oxygen demand and with this compensatory adenosine release, coronary flow is increased and ventricular function is unaffected (Am J Physiol 1996 ; 270 : H427-H434). Chronic inhibition of NO formation with oral administration of L-NAME for 4 weeks blunted coronary reactive hyperemia but did not substantially impair the coronary blood flow response to the increased myocardial oxygen requirement produced by atrial pacing. It was therefore indicated that adenosine is likely to play a role also in chronic model of NO synthesis inhibition (Jpn Cric J,1998, in press).