Urocortin舒张自发性高血压大鼠胸主动脉与NO和K~+通道的关系

目的探讨Urocortin(Ucn)对自发性高血压大鼠(SHR)胸主动脉舒缩功能的作用及机制。方法采用体外血管灌流,观察Ucn对SHR胸主动脉的舒张作用,以及左旋硝基精氨酸甲酯(N(ω)n itro-L-argin ine methyl ester,L-NAME)、亚甲蓝(M ethylene B lue,MB)和格列本脲(G lybenc lam ide)对其舒张作用的影响。结果Ucn(1 nmol.L-1~1μmol.L-1)可明显舒张内皮完整和去内皮SHR胸主动脉(P<0.01),此作用具有剂量依赖性;一氧化氮(NO)合成酶抑制剂L-NAME(100μmol.L-1)和鸟苷酸环化酶(GC)抑制剂MB部分抑制Ucn舒张血管的作用,而且增强去甲肾上腺素(NE)产生的收缩反应。ATP敏感钾通道(KATP)阻断剂格列本脲(10μmol.L-1)可减弱Ucn的舒血管作用。结论Ucn对SHR血管具有内皮依赖性和非内皮依赖性舒张作用,此作用部分是Ucn增加血管内皮细胞NO水平实现的,并且与NO-cGMP通路和KATP通道有关。

Roles of nitric oxide and K+ channels in urocortin-induced relaxation on SHR thoracic aorta

Aim To investigate the vasodilatory effect and the mechanisms of urocortin(Ucn) on the thoracic aorta of spontaneously hypertensive rats(SHR).Methods Rings cut from SHR thoracic aorta were used in vitro.The endothelium dependent and independent vasorelaxing effects of Ucn were measured.Furthermore,it was also explored whether the relaxing effects of Ucn were affected by N~((ω)) nitro-L-arginine methyl ester(L-NAME), methylene blue(MB) and glybenclamide.Results Ucn(1 nmol·L~(-1)～1 μmol·L~(-1)) caused concentration dependent relaxation in SHR thoracic aorta with endothelium and without endothelium(P<0.01);L-NAME(100 μmol·L~(-1)),the inhibitor of NOS and methylene blue(10 μmol·L~(-1)),the inhibitor of GTP-cyclase,partly blocked the Ucn-induced relaxation of SHR thoracic aorta.Glybenclamide(10 μmol·L~(-1)),the ATP-sensitive potassium channel inhibitor,also inhibited the Ucn-induced relaxation.Conclusion These findings suggest that Ucn can relax SHR thoracic aorta in endothelium dependent and independent manner.The vasodilatory effect of Ucn is partly achieved via activating the excretion of NO.Moreover,the vasorelaxing effect of Ucn is associated with NO-cGMP pathway and K_(ATP) channels.