Accelerated cardiac hypertrophy and renal damage induced by angiotensin II in adrenomedullin knockout mice.

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.