Impact of nitric oxide on adrenomedullin- and proadrenomedullin N-terminal 20 peptide-induced cardiac responses: action by alone and combined administration.

The cardiac effects of adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) as well as the possible signaling pathways were investigated. In the isolated perfused rat heart, infusion of AM (10(-11) to 10(-8) M) and PAMP(10(-11) to 10(-8) M) for 10 min, alone or in combination, induced concentration-dependent decreases in the left ventricular pressure (LVP), LVP +/- dp/dtmax of the hearts. The effects were attenuated by Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase. ADM and PAMP alone or in combinations increased the coronary fluid (CF), which could be antagonized by L-NAME. Pretreatment of H89, an inhibitor of protein kinase A (PKA), failed to alter the AM- or PAMP-induced decreases in LVP and LVP +/- dp/dtmax, but further promoted the AM or PAMP increased CF. The cAMP content in left cardiac ventricle was increased significantly by ADM infusions but not by PAMP. There was no statistical difference in cAMP contents with ADM administrated alone from those combined with ADM and PAMP. In conclusion, this study reveals that ADM and PAMP infused alone or in combinations inhibited the function of rat hearts in vitro, which may be partly involved with the NOS/NO pathway, rather than cAMP/PKA.