Roles of Adrenomedullin in Hypertension and Hypertensive Organ Damage

Abstract

Adrenomedullin (AM) is a bioactive peptide having a wide range of biological actions such as vasodilatation, natriuresis, diuresis and inhibition of aldosterone secretion. Various organs and tissues, including the myocardium, vascular wall and kidneys, produce AM, and AM is also present in the bloodstream. Plasma levels of AM were elevated in patients with essential or secondary hypertension as compared with normotensive controls. When infused in a relatively short period of time, AM reduced blood pressure in humans and experimental animals largely through vasodilatation. The blood pressure of transgenic mice overexpressing AM was lower than that of their wild-type littermates; while heterozygotes of AM knockout mice showed higher blood pressure, suggesting a role for endogenous AM in the regulation of blood pressure. Studies with cultured cardiac cells suggest a role for AM in inhibiting hypertrophy or fibrosis of the heart as an autocrine or paracrine factor. Animal experiment studies showed that either prolonged infusion or virally mediated overexpression of AM ameliorated the cardiovascular and renal damage associated with hypertension. Thus, a body of evidence accumulated in this field suggests that AM functions to counteract the elevation in blood pressure and progression of hypertensive organ damage.