Increased gene expression of adrenomedullin and adrenomedullin-receptor complexes, receptor-activity modifying protein (RAMP)2 and calcitonin-receptor-like receptor (CRLR) in the hearts of rats with congestive heart failure

Adrenomedullin is a vasodilator peptide produced in various organs, including heart and kidney. A novel adrenomedullin receptor complex has recently been identified, namely the calcitonin receptor-like receptor (CRLR) and receptor-activity modifying protein (RAMP) 2. In the present study, we have examined gene expression of RAMP2, CRLR and adrenomedullin in hearts and kidneys of rats with congestive heart failure caused by coronary artery ligation. Partial cloning was performed to determine the rat RAMP2 nucleotide sequence. Messenger RNA levels were then determined using competitive, quantitative reverse transcription-PCR techniques. Significantly increased expression levels (means +/- S.E.) of RAMP2, CRLR and adrenomedullin mRNA were found in the atrium (1.8 +/- 0.2-fold, 1.8 +/- 0.2-fold and 2.1 +/- 0.1-fold, respectively, compared with sham operated rats) and in the ventricle (1.4 +/- 0.1-fold, 1.3 +/- 0.03-fold and 3.0 +/- 0.5-fold respectively). On the other hand, expression levels of RAMP2, CRLR and adrenomedullin mRNAs were not significantly changed in the kidney. These findings suggest potential roles of locally-produced and locally-acting adrenomedullin in the failing heart.