Abstract P334: Persistent Adrenomedullin Derivative Inhibits Development of Hypertension [Session Title: Salt and Hypertension]

Human adrenomedullin (hAM) consists of a 52 amino acid peptide that is amidated and has a disulfide bond. The bioactive peptide hAM has a variety of physiological functions, such as vasodilatation, hormone secretion, neurotransmission, embryogenesis, wound healing and immunoregulation. hAM has shown several therapeutic effects in experimental models of various diseases, including ischemic heart disease, inflammatory bowel disease, stroke and retinochoroidal disease. However, these therapies required continuous administration of hAM as the half-life of native hAM is quite short in blood. To resolve these issues, the aim of this study was to synthesize novel hAM derivative, and to examine its effect in spontaneously hypertensive rats (SHR). First, we conjugated the hAM N-terminal with 60kDa polyethylene glycol (PEG) (60 kDa PEG-hAM). To demonstrate that PEG binds covalently to α-amino residue of the N-terminal tyrosine of hAM, 60 kDa PEG-hAM was digested with cyanogen bromide and the AM(6-52) thus obtained was confirmed by ion exchange chromatography and MALDI-MS. Next, to determine plasma hAM concentrations, either 60 kDa PEG-hAM (10 nmol/kg) or native hAM was administrated subcutaneously with Wistar rat. We compared hAM concentrations in the peripheral blood of rats after injection with either 60 kDa PEG-hAM or native hAM. The hAM concentrations in the 60 kDa PEG-hAM group after 1, 7 and 10 days were 2600, 740 and 280 pM, respectively. In contrast, the hAM concentrations in ...
Source: Hypertension - Category: Cardiology Authors: Tags: Poster Abstract Presentations Source Type: research