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, includi ng heart and kidney. A novel adrenomedullin receptor complex has recently b een identified, namely the calcitonin receptor-like receptor (CRLR) and rec eptor-activity modifying protein (RAMP) 2. In the present study, we have ex amined gene expression of RAMP2, CRLR and adrenomedullin in hearts and kidn eys of rats with congestive heart failure caused by coronary artery ligatio n. Partial cloning was performed to determine the rat RAMP2 nucleotide sequ ence. Messenger RNA levels were then determined using competitive, quantita tive reverse transcription-PCR techniques. Significantly increased expressi on levels (means +/- S.E.) of RAMP2, CRLR and adrenomedullin mRNA were foun d in the atrium (1.8 +/- 0.2-fold, 1.8 +/- 0.2-fold and 2.1 +/- 0.1-fold, r espectively, 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 ot her hand, expression levels of RAMP2, CRLR and adrenomedullin mRNAs were no t significantly changed in the kidney. These findings suggest potential rol es of locally-produced and locally-acting adrenomedullin in the failing hea rt.