Yang Jinghui, Li Juxiang, Geng Bin, Ren Yongsheng, Tang Chaoshu
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Dec 18;35(6):561-5.
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.
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.
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.
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.
研究肾上腺髓质素（ADM）和肾上腺髓质素原N端20肽（PAMP）单独或联合应用对离体大鼠心脏的影响以及其作用涉及的可能信号通路。
在离体大鼠心脏中，用四通道生理记录仪测定以不同浓度的ADM和/或PAMP灌注时心脏的左心室压力（LVP）、LVP±dp/dtmax、冠脉流量（CF）和心率（HR），然后测定心肌中的环磷酸腺苷（cAMP）含量。
用10⁻¹¹至10⁻⁸mol·L⁻¹的ADM或10⁻¹¹至10⁻⁸mol·L⁻¹的PAMP灌注后，离体心脏的LVP和LVP±dp/dtmax呈浓度依赖性逐渐降低，且在相同浓度下，PAMP的作用比ADM更强。当ADM和PAMP两者浓度低至10⁻¹¹至10⁻¹⁰mol·L⁻¹联合应用时，心脏参数的降低比单独应用ADM或PAMP时更明显。然而，当它们在10⁻⁹至10⁻⁸mol·L⁻¹的较高浓度联合应用时，ADM和PAMP的抑制作用减弱。当给大鼠心脏灌注ADM、PAMP以及ADM加PAMP时，CF总是高于对照组，而与一氧化氮合酶（NOS）抑制剂L-NAME联合应用时CF降低，但LVP和LVP±dp/dtmax的降低程度被L-NAME减弱。单独灌注ADM可使左心室中的cAMP含量显著增加，而PAMP灌注后无明显变化，单独灌注ADM的大鼠心脏与ADM和PAMP联合灌注的大鼠心脏相比，cAMP含量无统计学差异。
这些结果表明，单独或联合灌注ADM和PAMP可在体外抑制大鼠心脏功能，这可能部分与NOS/NO途径有关。
