Beresewicz A, Karwatowska-Prokopczuk E, Lewartowski B, Cedro-Ceremuåzyńska K
Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warsaw, Poland.
Cardiovasc Res. 1995 Dec;30(6):1001-8. doi: 10.1016/s0008-6363(95)00175-1.
The importance of NO-induced vasodilator tone in maintaining adequate coronary flow to sustain hemodynamic function in aerobically perfused heart and the role of NO in the injury development in ischaemic/reperfused heart was studied.
Effect of NO synthesis inhibitor (N omega-nitro-L-arginine, L-NOARG) on isolated working rat hearts subjected to either 90 min of aerobic perfusion or to a global ischaemia (27.5 to 42.5 min) followed by 40 min reperfusion was studied. To overcome coronary flow reducing effect of L-NOARG either perfusion pressure was raised from 75 to 120 cm H2O or adenosine (400 nM) was administered.
In the hearts perfused at coronary pressure of 75 and 120 cm H2O, L-NOARG (10 microM) reduced coronary flow by 30% and 17%, respectively, while cardiac output was not affected. Only a transient increase in adenosine and lactate outflow occurred in L-NOARG-treated hearts. The post-ischaemic recovery of functions was impaired in L-NOARG-treated hearts, an effect not correlating with L-NOARG-induced reduction in coronary flow. Although the pre-ischaemic coronary flow was similar in the untreated hearts perfused at 75 cm H2O and in L-NOARG-treated hearts perfused at 120 cm H2O, the post-ischaemic recovery in the latter group was still impaired as compared to that in the untreated hearts. Likewise, coronary flow was similar in the untreated hearts and in those treated with L-NOARG plus adenosine, nevertheless, the post-ischaemic recovery in the latter group was impaired as compared to that in the untreated hearts.
While the inhibition of NO synthesis resulted in coronary flow reduction it did not induce a state of permanent ischaemia in isolated rat heart. L-NOARG-induced augmentation of the ischaemia/reperfusion injury was related to the deficit of NO, itself, rather than to the reduction in myocardial perfusion.
研究一氧化氮（NO）诱导的血管舒张张力在维持有氧灌注心脏的冠状动脉血流量以维持血流动力学功能中的重要性，以及NO在缺血/再灌注心脏损伤发展中的作用。
研究了NO合成抑制剂（Nω-硝基-L-精氨酸，L-NOARG）对离体工作大鼠心脏的影响，这些心脏分别进行90分钟的有氧灌注或经历全心缺血（27.5至42.5分钟），随后再灌注40分钟。为克服L-NOARG对冠状动脉血流的减少作用，要么将灌注压力从75厘米水柱提高到120厘米水柱，要么给予腺苷（400纳摩尔）。
在冠状动脉压力为75和120厘米水柱下灌注的心脏中，L-NOARG（10微摩尔）分别使冠状动脉血流量减少30%和17%，而心输出量未受影响。L-NOARG处理的心脏中仅出现腺苷和乳酸流出的短暂增加。L-NOARG处理的心脏缺血后功能恢复受损，这种作用与L-NOARG诱导的冠状动脉血流量减少无关。尽管在75厘米水柱下灌注的未处理心脏和在120厘米水柱下灌注的L-NOARG处理心脏缺血前的冠状动脉血流量相似，但与未处理心脏相比，后一组的缺血后恢复仍受损。同样，未处理心脏和用L-NOARG加腺苷处理的心脏冠状动脉血流量相似，然而，与未处理心脏相比，后一组的缺血后恢复仍受损。
虽然NO合成的抑制导致冠状动脉血流量减少，但它并未在离体大鼠心脏中诱导永久性缺血状态。L-NOARG诱导的缺血/再灌注损伤加重与NO本身的缺乏有关，而不是与心肌灌注减少有关。
