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.