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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
Objective To investigate the effect of adrenomedullin precursor peptide on the regulation of aortic vascular tone by adrenomedullin (ADM) and to explore its possible mechanism. Methods The isolated rat thoracic aorta rings were pre-treated with phenylephrine and allowed to contract for maximal tension. After adding ADM, PAMP and ADT at different concentrations separately or in combination, their effects on the tension of isolated vascular rings were recorded ; ADM, PAMP and ADT were added separately or in combination to rat thoracic aorta incubated in vitro. Nitrite content, NOS activity in thoracic aorta and cAMP in thoracic aorta were measured. Results (1) ADM significantly reduced the tension of thoracic aortic rings contracted by 10 - 8M phenylephrine. The same concentration of PAMP and ADT had no obvious effect on the contraction of thoracic aortic rings by phenylephrine. PAMP dose-dependently reverses the vasorelaxant effect of ADM on blood vessels. ADT had no significant effect on the vasodilating effect of ADM. (2) ADM increased nitrite production and NOS activity in a concentration-dependent manner (P <0.05). PAMP and ADT alone incubated blood vessels, nitrite production and NOS activity compared with the control group no significant difference (P> 0 05). PAMP or ADT could significantly reduce the nitrite production induced by ADM and significantly reduce the NOS activity (P <0.01). (3) The levels of cAMP in the vessels of ADM, PAMP and ADT alone groups were significantly increased. Co-incubation of ADM with either PAMP or ADT significantly reduced cAMP levels in tissues (P <0.01). Conclusion ADM has the effect of relaxing blood vessels and stimulating NO release and NOS activity in rat aorta and