N－单甲基左旋精氨酸对犬冠脉内皮依赖性舒张功能及内皮素－1含量的影响

Effects of intracoronary NG -monomethyl-L-arginine on vasomotion and endothelium-dependent responses of coronary arteries and en-dothelin-1 levels in coronary circulation in anesthetized dogs

作者在开胸麻醉犬心脏上，观察冠脉内灌注Ｎ－单甲基左旋精氨酸（Ｌ－ＮＭＭＡ）５ｍｇ／ｋｇ，前后冠脉血流动力学、冠脉血流储备（以阻断冠脉１５ｓ再灌注所致的反应性充血血流峰值表示）以及冠脉对不同浓度乙酰胆硷（Ａｃｈ）反应的变化，同时用放射免疫法（ＲＩＡ）测定冠脉前降支（ＬＡＤ）伴行静脉血中的内皮素－１（ＥＴ－１）含量．结果证明，Ｌ－ＮＭＭＡ灌注后心率下降，基础冠脉血流量（ＣＢＦ）下降（χ±ｓ，从２７±６ｍｌ／ｍｉｎ下降至２０±８ｍｌ／ｍｉｎ，Ｐ＜０．０５），冠脉储备下降（χ±ｓ，从９１±１９ｍｌ／ｍｉｎ下降至５０±１０ｍｌ／ｍｉｎ，Ｐ＜０．０１），平均主动脉压升高，ＥＴ－１含量明显升高（χ±ｓ，从６．５±１．０ｎｇ／Ｌ升至１５．５±３．０ｎｇ／Ｌ，Ｐ＜０．０１），Ａｃｈ引起的ＣＢＦ增加减弱（Ｐ＜０．０１）．实验结果提示，生理条件下犬冠脉一氧化氮（ＮＯ）形成对ＣＢＦ，冠脉储备有重要调节作用，同时可抑制冠脉ＥＴ－１释放．

Peak reactive hyperemic coronary blood flow(CBF)following 15 s occlusion,resting CBF and CBF in response to acetylcholine(Ach)were obtained both before and after a 5 mg/kg intracoronary infusion of NG-monomethyl-L-arginine(L-NMMA) in open-chest anesthetized dogs.Meanwhile,serial endothelin-1 (ET-1)levels were obtained from the left interventricular vein and measured by radioimmunoassay.Results:L-NMMA induced a decrease in resting CBF(LAD)and peak reactive hyperemic LAD flow.Ach-stimulated endothelium-dependent responses were also attenuated after L-NMMA.There was an accompanying increase in aortic pressure and a decrease in heart rate.Changes in left ventricular end diatolic pressure and contractil-ity were not significant.An increase in left interventricular vein blood ET-1 was observed for 60 min after L-NMMA.These data support the view that nitric oxide plays a significant role in modulating basal coronary vasomotion,coronary blood reserve and endothelium-dependent dilation stimulated by Ach,and it also sup-presses cardiac release of ET-1 under physiologic conditions.