肾上腺髓质素前体肽不同肽段对大鼠离体主动脉血管环张力的影响

目的　观察肾上腺髓质素前体肽对肾上腺髓质素 (ADM )调节大鼠主动脉血管环张力的影响并探讨其可能的机制。方法　在孵育的大鼠离体胸主动脉环上予先加入苯肾上腺素使之收缩达最大张力后 ,单独或联合加入不同浓度的ADM、PAMP和ADT ,记录其对离体血管环张力的作用 ;在离体孵育的胸主动脉组织中 ,单独或联合加入不同浓度的ADM、PAMP和ADT ,测定孵育液亚硝酸盐含量、胸主动脉组织的NOS的活性和胸主动脉组织cAMP的水平。结果　 ( 1)ADM能显著降低由 10 - 8M的苯肾上腺素收缩的胸主动脉环的张力 ,浓度相同的PAMP和ADT对苯肾上腺素收缩的胸主动脉环张力没有明显的影响。PAMP可剂量依赖性地逆转ADM对血管的舒张效应。ADT对ADM的舒血管作用没有明显影响 ;( 2 )ADM浓度依赖性地增加亚硝酸盐的生成量和NOS的活性 (P <0 0 5)。PAMP和ADT单独孵育血管 ,其亚硝酸盐的生成量和NOS的活性与对照组相比无显著差异 (P >0 0 5)。PAMP或ADT能明显减少ADM所致的亚硝酸盐生成量和显著减弱NOS活性 (P值均 <0 0 0 1) ;( 3 )单独ADM、PAMP和ADT孵育血管明显增高组织中cAMP的水平。ADM和PAMP或ADT共同孵育血管明显降低组织中cAMP的水平 (P值均 <0 0 1)。结论　ADM具有舒张血管的作用和刺激大鼠主动脉NO释放和NOS活性的作用 ,并

Roles of Different Peptide Fragments Derived From Proadrenomedullin in the Regulation of Vascular Tone in Isolated Rat Aorta

Objective To investigate the effects of different peptides derived from proadrenomedullin, ADM, proadrenomedullin N terminal 20 peptide (PAMP), and adrenotensin (ADT) on vascular tone. Isolated rings from rat aorta with endothelium was used. cAMP accumulation and nitric oxide synthesis were also evaluated by measuring cAMP and the production of nitrite in cultured rat aorta tissue. Results Adrenomedullin(ADM) at concentrations of 1-100 nmol/L induced concentration depending relaxant responses. The same concentrations of PAMP or ADT had no effect on the aortic ring precontracted with phenylephrine. Co administration of ADM with ADT decreased the vascular tone, with no difference from that by ADM alone. Incubation of aortic tissue cultures with ADM (1-100 nmol/L) for 2 hours caused a significant increase in nitrite generation. This effect of adrenomedullin was abolished in the presence of PAMP or ADT. The ADM(10 nmol/L) induced nitrite production was decreased by PAMP (10 nmol/L) or ADT (10 nmol/L). The adrenomedullin induced nitrite production by aortic tissue was accompanied by nitric oxide synthase activity. ADM (1-100 nmol/L), incubated with the aortic tissue for 30 min, concentration dependently increased the cAMP levels of the vascular tissue. PAMP (10 nmol/L) and ADT (10 nmol/L), when administrated alone respectively, were more potent than the same concentration of ADM in stimulating cAMP accumulation. Co administrated of ADM with PAMP or ADT, the cAMP accumulation was further increased as compared with that of ADM alone, but the effect of PAMP and ADT on ADM was not additive or synergistic but an antagonist one. These results of the present study demonstrated that ADM caused vasodilatation of isolated aortic ring constricted with phenylephrine. The relaxing effect of ADM on the aortic ring can be antagonized by PAMP, whereas ADT had no effect on the ADM induced vascular relaxant effect. ADM augments the nitric oxide synthesis in the aortic vascular tissue, which can be inhibited by PAMP or ADT. This effect of PAMP on ADM induced vasorelaxation, probably through a NO dependent pathway.