Gold M E, Wood K S, Buga G M, Byrns R E, Ignarro L J
Department of Pharmacology, UCLA School of Medicine 90024.
Biochem Biophys Res Commun. 1989 Jun 15;161(2):536-43. doi: 10.1016/0006-291x(89)92632-6.
This study examined the actions of L-arginine, a putative precursor of endothelium-derived nitric oxide, and arginine analogs on endothelium-dependent relaxation of isolated rings of bovine pulmonary artery. L-Arginine did not consistently relax arterial rings unless rings were first rendered refractory to endothelium-dependent relaxation by pretreatment with 1 microM A23187 for 45 min. L-Arginine-elicited relaxation was endothelium-dependent, antagonized by oxyhemoglobin or methylene blue, and unaffected by indomethacin. L-Argininosuccinic acid caused endothelium-dependent contractions and irreversible inhibition of endothelium-dependent but not nitroglycerin-elicited relaxation, which was not overcome by addition of L-arginine. Inhibition of endothelium-dependent relaxation by L-NG-monomethyl arginine, however, was reversible and overcome by L-arginine. Therefore, endothelium-dependent relaxants may cause arginine depletion in endothelial cells and endogenous argininosuccinic acid may modulate the biosynthesis of endothelium-derived nitric oxide from arginine.
本研究检测了L-精氨酸（一种推测的内皮源性一氧化氮前体）及其精氨酸类似物对离体牛肺动脉环内皮依赖性舒张的作用。除非先用1微摩尔/升A23187预处理45分钟使血管环对内皮依赖性舒张产生不应性，否则L-精氨酸并不能持续舒张动脉环。L-精氨酸引发的舒张是内皮依赖性的，可被氧合血红蛋白或亚甲蓝拮抗，且不受吲哚美辛影响。L-精氨琥珀酸引起内皮依赖性收缩，并对内皮依赖性舒张产生不可逆抑制，但对硝酸甘油引发的舒张无影响，添加L-精氨酸也无法克服这种抑制。然而，L-NG-单甲基精氨酸对内皮依赖性舒张的抑制是可逆的，可被L-精氨酸克服。因此，内皮依赖性舒张剂可能导致内皮细胞中的精氨酸耗竭，内源性L-精氨琥珀酸可能调节由精氨酸生成内皮源性一氧化氮的生物合成过程。
