title: Accelerated cardiac hypertrophy and renal damage induced by angiotensin II in adrenomedullin knockout mice.
abstract: Adrenomedullin (AM) is a potent vasodilating and natriuretic peptide that is thought to play important roles in cardiovascular function. Whether or not AM is involved in the development of cardiac hypertrophy and renal damage remains controversial. In the present study, using heterozygote knockout mice of the AM gene (AM +/-), we analyzed the physiological and pathological roles of the endogenous AM gene. There were no differences in body size or heart and kidney weight compared with wild-type (AM +/+) mice. However, angiotensin II (Ang II) infusion resulted in more severe cardiac hypertrophy in AM +/- mice. The increases in the heart weight-to-body weight ratio and wall thickness of the left ventricle were more prominent in the AM +/- mice. Renal dysfunction characterized by decreased creatinine clearance (C(cr)) was more severe in AM +/- after Ang II infusion. These results suggest that AM plays critical roles in the defense mechanism against cardiac hypertrophy and renal dysfunction. An improved understanding of these roles may pave the way to a novel pharmacological approach for the prevention of cardiovascular diseases.
authors: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Pei
authors: P
authors: Niu
authors: Takayuki
authors: T
authors: Shindo
authors: Hiroshi
authors: H
authors: Iwata
authors: Aya
authors: A
authors: Ebihara
authors: Yoshihiro
authors: Y
authors: Suematsu
authors: Yuelan
authors: Y
authors: Zhang
authors: Norifumi
authors: N
authors: Takeda
authors: Satoshi
authors: S
authors: Iimuro
authors: Yasunobu
authors: Y
authors: Hirata
authors: Ryozo
authors: R
authors: Nagai
mesh_terms: D053607:Adrenomedullin; D000804:Angiotensin II / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects*; D014665:Vasodilator Agents / Q000378:metabolism*
chemical_list: D010455:Peptides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D053607:Adrenomedullin