Adrenomedullin 2/intermedin (AM2/IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family. To investigate the pathophysiological role of AM2/IMD in heart failure, we examined the expression of AM2/IMD, adrenomedullin (AM) and receptor complex components (calcitonin receptor-like receptor, three types of receptor activity-modifying proteins) by quantitative RT-PCR and immunohistochemistry in the hearts and kidneys of rats with congestive heart failure (CHF). Significantly increased levels of AM2/IMD mRNA were found in the atrium, right ventricle, non-infarcted part of the left ventricle and the infarcted part of the left ventricle of CHF rats, compared with sham operated rats (about 2.8-fold, 1.7-fold, 1.7-fold and 2.5-fold, respectively). Expression levels of mRNA encoding AM and the receptor complex components were also increased in the hearts of CHF rats. In a separate experiment, AM2/IMD mRNA levels in the heart did not differ between Wistar-Kyoto and spontaneously hypertensive rats. In both sham operated and CHF rats, the myocardium was diffusely immunostained with AM2/IMD. The fibrotic infarcted layer was not immunostained with AM2/IMD but was surrounded by positively immunostained myocardial layers. These findings suggest that the expression of AM2/IMD is enhanced in the failing heart, and AM2/IMD has a certain pathophysiological role in heart failure.

Adrenomedullin 2/intermedin (AM2/IMD) is a novel vasodilator peptide with various effects on the renal function and cardiovascular system. An exonic insertion (I)/deletion (D) polymorphism (rs3840963) may influence generation of AM2/IMD-53, due to its location within the N-terminal sequence. We investigated the association of this polymorphism with blood pressure, renal function and the risk of silent cerebrovascular lesions in a Japanese population recruited from the Ohasama study. We recorded 24 h ambulatory blood pressure (ABP), estimated glomerular filtration rate (eGFR) and proteinuria of 1073 individuals over 40 years of age. Silent cerebrovascular lesions (lacunar infarction and white matter hyperintensity (WMH)) were recorded in 794 individuals over 55 years of age. Chronic kidney disease (CKD) was diagnosed in individuals with proteinuria and/or decreased eGFR p60 ml min À1 per 1.73 m 2 . DD carriers, compared with II and ID carriers, displayed significantly higher 24 h ABP (127.4 vs. 122.0 and 122.9 mm Hg, respectively, in systolic ABP, P¼0.009; and 74.8 vs. 71.3 and 72.5 mm Hg, respectively, in diastolic ABP, P¼0.002), and lower eGFR (75.4 vs. 82.6 and 82.9 ml min À1 per 1.73 m 2 , respectively, P¼0.04). DD carriers also had a significantly higher odds ratio (OR) for prevalence of CKD (OR: 2.7, P¼0.003), presence of lacunar infarction (OR: 2.4, P¼0.01) and WMH (OR: 2.7, P¼0.003), compared with II carriers. The AM2/IMD I/D polymorphism is associated with renal dysfunction, blood pressure regulation and asymptomatic cerebrovascular diseases in the Japanese general population.