Lot T Y
Department of Physiology and Pharmacology, Faculty of Medicine, Queen's Medical Centre, University of Nottingham, United Kingdom.
Arch Int Pharmacodyn Ther. 1993 May-Jun;323:62-73.
The possibility that guanidino succinic acid is the major endogenous source of endothelium-derived relaxing factor has been examined using the porcine isolated splenic artery. Administration of 100 microM NG-nitro-L-arginine methyl ester (L-NAME) caused a substantial, endothelium-dependent contraction of the splenic artery that was inhibited by L-arginine (1 mM) but was unaffected by D-arginine (1 mM). L-NAME enhanced the responsiveness of the splenic artery to 5-hydroxytryptamine in endothelium-intact segments only, and the potentiating action of L-NAME was inhibited by L-arginine but not by D-arginine. Administration of 100 microM guanidino succinic acid did not relax the splenic artery and it did not inhibit or reverse contractions of the splenic artery induced by L-NAME. Administration of guanidino succinic acid, either before or after L-NAME, did not affect the potentiating action of L-NAME on the 5-hydroxytryptamine-induced contraction of the splenic artery in endothelium-intact segments. Although substance P caused an endothelium-dependent relaxation of preconstricted segments of the splenic artery, guanidino succinic acid did not relax preconstricted, endothelium-intact or endothelium-denuded segments of the artery. L-NAME inhibited the relaxation induced by substance P in endothelium-intact preparations. The findings for the effects of arginine are consistent with L-arginine being a source of endothelium-derived relaxing factor in the porcine splenic artery, while observations with guanidino succinic acid indicate that it is not a substrate for the synthesis of endothelium-derived relaxing factor in this blood vessel.
利用猪离体脾动脉，研究了胍基琥珀酸作为内皮源性舒张因子主要内源性来源的可能性。给予100微摩尔/升的N G-硝基-L-精氨酸甲酯（L-NAME）可引起脾动脉显著的、内皮依赖性收缩，L-精氨酸（1毫摩尔/升）可抑制该收缩，但D-精氨酸（1毫摩尔/升）对其无影响。L-NAME仅增强了内皮完整节段中脾动脉对5-羟色胺的反应性，且L-NAME的增强作用被L-精氨酸抑制，但不被D-精氨酸抑制。给予100微摩尔/升胍基琥珀酸并未使脾动脉舒张，也未抑制或逆转L-NAME诱导的脾动脉收缩。在L-NAME之前或之后给予胍基琥珀酸，均不影响L-NAME对内皮完整节段中5-羟色胺诱导的脾动脉收缩的增强作用。尽管P物质可引起脾动脉预收缩节段的内皮依赖性舒张，但胍基琥珀酸并未使动脉的预收缩、内皮完整或内皮剥脱节段舒张。L-NAME抑制了内皮完整制剂中P物质诱导的舒张。精氨酸作用的研究结果与L-精氨酸作为猪脾动脉内皮源性舒张因子的来源一致，而胍基琥珀酸的观察结果表明，它不是该血管中内皮源性舒张因子合成的底物。
