Pieper G M, Dondlinger L A
Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee Wisconsin 53226, USA.
J Pharmacol Exp Ther. 1997 Nov;283(2):684-91.
Arginine is a precursor amino acid for the synthesis of nitric oxide by nitric oxide synthase. A defect in arginine supply could regulate nitric oxide-mediated, endothelium-dependent relaxation. In this study, we evaluated the effect of supplementation with L-arginine given in vitro on both functional relaxation and cGMP generation in response to acetylcholine in the streptozotocin-induced diabetic rat aorta. The concentration of arginine in plasma and aortic tissue were both decreased by diabetes. Acute incubation in vitro with L-arginine augmented the impaired relaxation to acetylcholine in diabetic rings although not altering relaxation in control rings. L-Arginine also enhanced relaxation to acetylcholine in diabetic rings incubated in the presence of either indomethacin or tetraethylammonium to inhibit cyclooxygenase activity and potassium channel activity, respectively. Acetylcholine-stimulated cGMP generation (which was blocked by L-nitroarginine) was diminished in diabetic rings compared with control rings. L-Arginine restored cGMP in diabetic rings (with but not without endothelium) to levels similar to control rings. L-Arginine did not alter cGMP generated by nitroglycerin. Incubation with L-arginine had no effect on acetylcholine-stimulated cGMP generation in control rings (with and without endothelium). These data suggest a potential intracellular substrate deficiency in nitric oxide production by diabetic endothelium which can be overcome acutely in vitro by provision of substrate for nitric oxide synthase.
精氨酸是一氧化氮合酶合成一氧化氮的前体氨基酸。精氨酸供应缺陷可能会调节一氧化氮介导的内皮依赖性舒张。在本研究中，我们评估了体外补充L-精氨酸对链脲佐菌素诱导的糖尿病大鼠主动脉中乙酰胆碱引起的功能性舒张和环鸟苷酸（cGMP）生成的影响。糖尿病会使血浆和主动脉组织中的精氨酸浓度均降低。体外急性孵育L-精氨酸可增强糖尿病血管环对乙酰胆碱受损的舒张反应，尽管对对照血管环的舒张无影响。在分别存在吲哚美辛或四乙铵以抑制环氧化酶活性和钾通道活性的情况下孵育的糖尿病血管环中，L-精氨酸也增强了对乙酰胆碱的舒张反应。与对照血管环相比，糖尿病血管环中乙酰胆碱刺激的cGMP生成（被L-硝基精氨酸阻断）减少。L-精氨酸使糖尿病血管环（有内皮和无内皮）中的cGMP恢复到与对照血管环相似的水平。L-精氨酸不改变硝酸甘油产生的cGMP。在对照血管环（有内皮和无内皮）中，与L-精氨酸孵育对乙酰胆碱刺激的cGMP生成无影响。这些数据表明糖尿病内皮细胞在产生一氧化氮方面可能存在潜在的细胞内底物缺乏，在体外通过为一氧化氮合酶提供底物可急性克服这一情况。
