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）在冠状动脉血流调节中的作用，我们在麻醉犬中进行了体内研究。已经揭示，EDNO在基础冠状动脉血流量的调节中起作用（Arch int Pharmacodyn 1994 ; 327：251-265），并且心肌反应性充血（RH）不仅由腺苷介导，而且由EDNO介导（Am J Physiol 1992 ; 263：H4-H14）。最近，我们研究了锰（Mn）-超氧化物歧化酶（SOD）对麻醉犬RH的影响，发现在缺血60 s和再灌注过程中产生的超氧化物自由基通过灭活EDNO来降低心肌RH（心血管研究1996 ; 31：537-545）。Mn-SOD对心肌RH的作用比Cu，Zn-SOD更明显。腺苷释放响应于心肌需氧量而增加，并且随着这种补偿性腺苷释放，冠状动脉流量增加，心室功能不受影响（AmJPhysiol 1996 ; 270：H427-H434）。长期口服L-NAME抑制NO形成4周可减弱冠状动脉反应性充血，但对心房起搏引起的心肌需氧量增加的冠状动脉血流反应无明显影响。因此表明腺苷可能在NO合成抑制的慢性模型中也起作用（Jpn Cric J，1998，出版中）。

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).