Upregulated expression of intermedin and its receptor in the myocardium and aorta in spontaneously hypertensive rats

Abstract

Intermedin (IMD), also called adrenomedullin 2 (ADM2), is a 47-amino acid peptide belonging to the calcitonin/calcitonin gene-related peptide (CGRP) family. IMD has similar or more potent vasodilatory and hypotensive actions compared with adrenomedullin (ADM) and CGRP. This study was designed to explore the role of IMD and its receptor in the pathogenesis of spontaneous hypertension and cardiac hypertrophy. Radioimmunoassay was employed to determine plasma immunoreactive IMD concentration and tissue immunoreactive IMD levels in the myocardium and aorta as well as cAMP concentration in the cardiovascular tissues in 13-week-old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). The mRNA expression of IMD, its receptor, calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP)) were determined by semi-quantitative RT-PCR. Protein levels of CRLR and RAMPs were assayed by Western blotting. Our results showed that immunoreactive IMD concentration was enhanced in the SHR myocardium, aortas and plasma. Both the mRNA and protein levels of IMD, as well as those of CRLR and RAMP 1–3 were upregulated in SHRs. IMD affected cAMP generation in the myocardium and aorta, which were not attenuated by prior addition of either CGRP 8–37 or ADM 22–52 alone. These results indicate that the elevation of IMD and its receptor in the cardiovascular tissue may play an important role in the pathogenesis of spontaneous hypertension.