L-精氨酸及其N衍生物对高血压大鼠离体血管的舒张作用

Vasodilation Effects of L-arginine and Its Analogues on Isolated Aortic Rings in Spontaneously Hypertensive Rats

用L-精氨酸及L-精氨酸N端α衍生物N-乙酰精氨酸、N-苯甲酰精氨酸,对原发性高血压大鼠离体主动脉血管平滑肌的舒张作用进行研究,并与正常血压大鼠的主动脉血管平滑肌做比较。结果发现,L-精氨酸、N-乙酰精氨酸、N-苯甲酰精氨酸、和具有精氨酸-甘氨酸-天冬氨酸,即RGD序列的短肽精氨酸-甘氨酸-天冬氨酸-苯乙酰胺（RGD-PEA）,对于高血压及正常血压大鼠离体主动脉血管平滑肌均有程度不等的舒张作用,且显示剂量依赖性和内皮依赖性。药效动力学分析表明,舒张血管的半数有效浓度除RGD-PEA在10^(-6)mol/L之外,其余的均在10^(-7)mol/L范围;L-Arg及其N衍生物对高血压大鼠主动脉的最大舒张效应在4％～20％范围。

This study was designed to investigate the effects of L-arginine(the substrate for the formation of endothelium aerived nitric oxide) and its analogues N-Ac-L-Arginine(Ac-Arg) ,N-benzoyl-L-argi-nine(Be-Arg) and peptide with RGD sequence Ac-Arg-Gly-Asp-NHC2H4C6H5 (RGD-PEA) in vascular tissues of normotensive and hypertensive rats. Rat aortic rings, with or without endothelium were suspended in organ chambers for the measurement of isometric tension. L-arginine and its analogues evoked concentration-dependent relaxation in aortic rings both with and without endothelium ranged at 10-9 to 10-3mol/L. The pharmacodynamic parameters indicated that the half effective concentrations (EC50) were about 10-7 for L-arginine and Ac-Arg,Be-Arg.4%-20% increases in vasodilation seem to be the maximal effect of both L-arginine and RGD-PEA. The results suggested that L-arginine and its analogues may play a role in the regulation of blood pressure and possible therapeutic effect for hypertension.