Archibald V, Cotter M A, Keegan A, Cameron N E
Department of Biomedical Sciences, University of Aberdeen, Marischal College, Scotland, UK.
Naunyn Schmiedebergs Arch Pharmacol. 1996 Apr;353(5):584-91. doi: 10.1007/BF00169180.
We examined whether chronic treatment with the free radical scavengers butylated hydroxytoluene (1 g kg-1 day-1) and N-acetyl-L-cysteine (250 mg kg-1 day-1), or the inhibitor of advanced glycosylation reactions, aminoguanidine (1 g kg-1 day-1), could prevent the development of relaxation and contraction abnormalities in aorta from 2 month streptozotocin-diabetic rats. Diabetes caused a 24% deficit in maximal endothelium-dependent relaxation to acetylcholine for phenylephrine precontracted aortas (P < 0.01). This was unaffected by tissue-bath glucose concentration (5.5 or 40 mM), or by addition of 1 mM L-arginine. Butylated hydroxytoluene, N-acetyl-L-cysteine and aminoguanidine treatments gave substantial protection, maximum relaxation remaining in the non-diabetic range. Neither diabetes nor treatment affected endothelium-independent relaxation to glyceryl trinitrate. To test the suggestion that aminoguanidine could act as an inhibitor of constitutive nitric oxide synthase, acute aminoguanidine effects on endothelium-dependent relaxation to acetylcholine were also examined. No inhibition was noted. A modest increase in phenylephrine sensitivity with diabetes (P < 0.05) was unaffected by butylated hydroxytoluene or N-acetyl-L-cysteine, but partially prevented by aminoguanidine (P < 0.05). The data, therefore, provide evidence for the involvement of reactive oxygen species and the advanced glycosylation process particularly for impaired endothelium-dependent relaxation in experimental diabetes.
我们研究了用自由基清除剂叔丁基对苯二酚（1克/千克/天）和N-乙酰-L-半胱氨酸（250毫克/千克/天），或晚期糖基化反应抑制剂氨基胍（1克/千克/天）进行长期治疗，是否能预防链脲佐菌素诱导的糖尿病大鼠2个月后主动脉舒张和收缩异常的发生。糖尿病导致苯肾上腺素预收缩的主动脉对乙酰胆碱的最大内皮依赖性舒张功能降低24%（P<0.01）。这不受组织浴葡萄糖浓度（5.5或40毫摩尔）或添加1毫摩尔L-精氨酸的影响。叔丁基对苯二酚、N-乙酰-L-半胱氨酸和氨基胍治疗提供了显著的保护作用，最大舒张功能保持在非糖尿病范围内。糖尿病和治疗均不影响对硝酸甘油的非内皮依赖性舒张。为了检验氨基胍是否可作为组成型一氧化氮合酶抑制剂的假设，还研究了氨基胍对乙酰胆碱内皮依赖性舒张的急性影响。未观察到抑制作用。糖尿病使苯肾上腺素敏感性适度增加（P < 0.05），叔丁基对苯二酚或N-乙酰-L-半胱氨酸对此无影响，但氨基胍可部分预防（P < 0.05）。因此，这些数据为活性氧和晚期糖基化过程参与实验性糖尿病中内皮依赖性舒张受损提供了证据。
