Role of endogenous adrenomedullin system in rat cardiac fibroblasts

Abstract Background: We investigated the effects of interleukin 1-beta (IL-1b) on the adrenomedullin system in cardiac fibroblasts and also examined the role of it. Methods: With or without the presence of IL-1b in cultured rat neonatal cardiac fibroblasts, we measured; (1) two molecular forms of adrenomedullin in cultured medium by specific immunoradiometric assay, (2) gene expression of adrenomedullin, calcitonin receptor like receptor (CRLR), receptor activity modifying protein2 (RAMP2), and RAMP3, which are components of adrenomedullin receptor, by northern blot analysis or RT-PCR, (3) cAMP levels in response to exogenous administered adrenomedullin, (4) 3 H-proline incorporation with and without a specific antisense oligodeoxynucleotide. Results: (1) IL-1b dose-dependently increased the levels of two molecular forms of adrenomedullin, adrenomedullin-mature and adrenomedullin-glycine (P −7 M (+26%, P 3 H-proline incorporation and adrenomedullin antisense oligodeoxynucleotide treatment further increased 3 H-proline incorporation (+22%, P Conclusion: These results support a physiological role for adrenomedullin in the regulation of cell growth as an autocrine factor in cardiac fibroblasts.