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(Circulation Research. 2002;90:625.)
© 2002 American Heart Association, Inc.

Editorials

Adrenomedullin

An Autocrine/Paracrine Factor for Cardiorenal Protection

Toshihiro Tsuruda, John C. Burnett, Jr

From the Mayo Clinic, Rochester, Minn.

Correspondence to John C. Burnett, Jr, MD, Cardiorenal Research Laboratory, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail burnett.john@mayo.edu

Key Words: adrenomedullin • transgenic • knockout • autocrine • paracrine

Since 1993, with the discovery of adrenomedullin (AM) by Kitamura and coworkers,¹ we have gained many insights into the biology of this new peptide. Although AM was originally found in human pheochromocytoma, preproAM gene expression and its immunoreactivity are widely distributed in humans and rodents and found in cardiovascular tissues, kidney, digestive organs, nervous system, and tumor cells.^2–4 While this ubiquitous AM distribution has prompted many investigators to clarify the role of AM, we advance the concept that the role of endogenous AM is especially important in cardiovascular and renal homeostasis. We now know that AM circulates in plasma and is present in organs and tissues with increases in AM activity in heart failure, hypertension, and renal dysfunction.^5,6 Although AM synthesis may be mainly regulated by lipopolysaccharide (LPS) and cytokines, it has been reported that hormones, as well as physical stimuli, stimulate AM synthesis in smooth muscle cells (SMCs), endothelial cells (ECs), and cardiomyocytes.^7–12 It is also accepted that AM has multiple functional properties linked to intracellular cyclic adenosine monophosphate (cAMP) elevation. Indeed, exogenous AM administration induces vasodilation and natriuresis with cAMP elevation, resulting in beneficial cardiorenal response in humans with heart failure.¹³ Although AM was originally found by monitoring cAMP elevation in platelets,¹ supporting a key role for cAMP, it has been reported that the nitric oxide (NO)-cGMP pathway also contributes to actions of AM.¹⁴ In addition, a third pathway might mediate the AM signal.¹⁵

AM as an Autocrine or Paracrine Factor

To date, the role of AM as an autocrine or paracrine factor has been . . . [Full Text of this Article]

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