Effects of Adrenomedullin

Exogenously administered adrenomedullin is mitogenic to cultured aortic VSMCs through p42/p44 ERK/MAPK pathway activation (33). Endogenous adrenomedullin secreted from cultured cardiac myocytes inhibits myocyte hypertrophy, demonstrating that it may act in an autocrine and/or a paracrine manner (31). In addition to effects on cell growth and hypertrophy, adrenomedullin promotes IL-6 secretion and attenuates endo-thelin-1 (ET-1) secretion from fibroblasts but not myocytes, as well as augments cyclic adenosine monophosphate (cAMP) production in response to IL-1^ (28). Adrenomedullin induces the secretion of IL-6 from cultured fibroblasts through a cAMP-mediated pathway and augments the TNF-a and IL-1-induced secretion of IL-6 and NO production (27). When administered in vivo directly into the coronary artery of instrumented sheep, adreno-medullin causes sustained coronary vasodilation, which is abolished with intracoronary infusion of A-nitro-l-arginine, a NO synthase inhibitor, demonstrating that the coronary vasodilation in response to adrenomedullin is mediated by the release ofNO from ECs (34).

Several studies have shown that plasma adrenomedullin concentrations are increased in patients with AMI (35-37), chronic heart failure (38), and hypertension (39), indicat-

Fig. 5. Kaplan-Meier survival curves for subgroups with early postinfarction plasma peptide (adreno-medullin [ADM] and norepinephrine [NE]) concentrations above (solid lines) and below (dashed lines) group median in 121 patients with MI. (Reproduced from ref. 37.)

ing the potential usefulness of adrenomedullin as a biomarker in conditions of hemodynamic stress.

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