{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T06:49:25Z","timestamp":1762066165952,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T00:00:00Z","timestamp":1662854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016924","name":"Intramural Research Fund","doi-asserted-by":"publisher","award":["21-3-2"],"award-info":[{"award-number":["21-3-2"]}],"id":[{"id":"10.13039\/100016924","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Plasma adrenomedullin concentrations are reportedly elevated in patients with renal failure; however, the underlying mechanism is unclear. In this study, we investigated the plasma clearance of synthetic human adrenomedullin (AM) in two models of rats with renal dysfunction; one was induced by subcutaneous injection of mercury chloride (RD-Ag) and the other by completely blocking bilateral renal blood flow (RD-Bl). Sixty minutes after starting intravenous AM infusion, AM levels in RD-Ag, RD-Bl, and rats with normal renal function (NF) were still increased slightly; however, plasma AM levels in RD-Ag rats were approximately three times as high as in RD-Bl and NF rats. Plasma AM disappearance after the end of treatment was similar among the three groups. Pharmacokinetic analysis revealed that elevated plasma AM in RD-Ag rats may be caused by a reduced volume of distribution. The adrenomedullin functional receptor is composed of heterodimers, including GPCR, CLR (calcitonin receptor-like receptor, CALCRL), and the single transmembrane proteins, RAMP2 or RAMP3 (receptor activity modifying protein). Calcrl expression was downregulated in the lungs and kidneys of RD-Ag rats. Furthermore, the plasma concentration of exogenous AM was elevated in mice deficient in vascular endothelium-specific Ramp2. These results suggest that decreased plasma AM clearance in RD-Ag is not due to impaired renal excretion but to a decreased volume of distribution caused by a reduction in adrenomedullin receptors.<\/jats:p>","DOI":"10.3390\/biom12091281","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T20:52:25Z","timestamp":1663015945000},"page":"1281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Plasma Clearance of Intravenously Infused Adrenomedullin in Rats with Acute Renal Failure"],"prefix":"10.3390","volume":"12","author":[{"given":"Hiroshi","family":"Hosoda","sequence":"first","affiliation":[{"name":"Department of Hypertension and Nephrology, National Cerebral and Cardiovascular Center Hospital, 6-1 Kishibe-Shimmachi, Suita 564-8565, Osaka, Japan"},{"name":"Department of Molecular Pathophysiology, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Nagano, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiki","family":"Yoshihara","sequence":"additional","affiliation":[{"name":"Department of Hypertension and Nephrology, National Cerebral and Cardiovascular Center Hospital, 6-1 Kishibe-Shimmachi, Suita 564-8565, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1006\/bbrc.1993.1451","article-title":"Adrenomedullin: A novel hypotensive peptide isolated from human pheochromocytoma","volume":"192","author":"Kitamura","year":"1993","journal-title":"Biochem. 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