肾上腺髓质素和肾上腺髓质素原N端20肽对大鼠离体灌流心脏功能的影响

目的 :研究肾上腺髓质素原 (proadrenomedullin ,proADM)的不同肽段 ,肾上腺髓质素 (adrenomedullin ,ADM )和肾上腺髓质素原N端 2 0肽 (proadrenomedullinN terminal 2 0 peptide ,PAMP)的心脏效应及可能机制。方法 :Langendorff装置灌流离体大鼠心脏 ,通过心室内的乳胶水囊经换能器连于PowerLab多导生理记录仪 ,观察不同浓度的ADM和PAMP对左心室内压 (leftventricularpressure ,LVP)、左室内压变化速率 (leftventricularpressure(dp/dtmax)、冠状动脉 (冠脉 )流量 (coronaryfluid ,CF)和心率 (heartrate,HR)的影响 ,并检测灌流后心肌组织cAMP含量。结果 :ADM (1 0 -1 1 ～ 1 0 -8mol·L-1 )灌流呈浓度依赖地降低心脏LVP和±dp/dtmax ;PAMP也以浓度依赖的方式降低上述心功能的指标 ,且较相同浓度的ADM作用强。PAMP与ADM依次以不同浓度梯度联合应用 ,较各药单用对上述心功能指标的影响表现为低浓度 (1 0 -1 1 ～ 1 0 -1 0 mol·L-1 )时增强 ,而高浓度 (1 0 -9～ 1 0 -8mol·L-1 )削弱其心功能抑制效应。ADM和PAMP单独或联合应用时 ,冠脉流量均高于对照组水平。灌流液含有NO合酶 (nitricoxidesynthase ,NOS)抑制剂L NAME(Nω nitro L argininemethylester)时 ,ADM、PAMP或ADM联合PAMP灌流 ,其对LVP、±dp

Effects of adrenomedullin and proadrenomedullin N-terminal 20 peptide, alone or in combination, on the rat hearts in vitro

OBJECTIVE: To study the effects of adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) alone or in combinations on the isolated rat hearts as well as the possible signaling pathways involved in their actions. METHODS: In isolated rat hearts the left ventricular pressure (LVP), LVP+/-dp/dtmax, coronary fluid (CF) and heart rate(HR) of the hearts infused at different concentrations of ADM and/or PAMP were determined by a 4-cannal physiological recorder, then the cAMP contents were assayed in myocardium. RESULTS: After being infused with ADM from 10(-11) to 10(-8) mol x L(-1) or PAMP from 10(-11) to 10(-8)mol x L(-1), the LVP and LVP+/-dp/dtmax of the isolated hearts decreased gradually in a concentration-dependent manner, and at the same concentration, the effects of PAMP were more potent than those of the ADM. When ADM and PAMP were co-administrated with both concentrations as low as from 10(-11) to 10(-10) mol x L(-1), the cardiac parameters were decreased more than either ADM or PAMP administrated alone. However, the inhibitory effects of ADM and PAMP were attenuated when they were in combination at higher concentrations as from 10(-9) to 10(-8) mol x L(-1). When the rat hearts were infused with ADM PAMP and ADM plus PAMP, the CF were always higher than those of the controls and decreased when co-administrated with L-NAME, an inhibitor of NOS, but the decreased degree of LVP and LVP+/-dp/dtmax were attenuated by L-NAME.The cAMP contents in the left cardiac ventricle were increased significantly by ADM infusions but not changed obviously by PAMP, and were of no statistical difference in rat hearts with ADM administrated alone from those combinated with ADM and PAMP. CONCLUSION: These results showed that ADM and PAMP infused alone or in combinations inhibited the function of rat hearts in vitro, which might be partly involved with the NOS/NO pathway.