• Adrenomedullin

    Adrenomedullin

    Essential player in septic shock
    The vasoactive hormone is highly elevated during sepsis progression
    and is the strongest known predictor of circulatory breakdown and death

Adrenomedullin

Adrenomedullin – an essential player in septic shock

Since its discovery in 1993, the vasoactive peptide hormone Adrenomedullin (ADM) has attracted great deal of interest from researchers due to its involvement in various vascular processes, including angiogenesis and cardiovascular homeostasis [3]. Adrenomedullin is mainly expressed and secreted by vascular endothelial cells and is well known for its strong vasodilatory activity [3]. Elevated ADM plasma levels correlate with the relaxation of vascular tone in patients with septic shock and are associated with increased mortality [4,5]. Most recently, it was demonstrated that adrenomedullin binding attenuates acute kidney injury in murine septic shock [6].

 

  Molecular mechanism of action

Adrenonomedullin exerts its molecular action mainly via the stimulation of cAMP formation and subsequent release of nitric oxide (NO) from vascular endothelial cells. The released NO in turn induces the relaxation of vascular smooth muscles. ADM binds the G protein–coupled receptor CRLR (calcitonin receptor-like receptor) that is expressed both on vascular smooth muscle and vascular endothelial cells. CRLR is associated with one of three different accessory single-pass transmembrane proteins called RAMP1-3 [7]. ADM only interacts with CRLR receptors that are accompanied by either RAMP2 or RAMP3 [7]. In addition to NO release, binding of Adrenomedullin to CRLR/RAMP2 or CRLR/RAMP3 on endothelial cells triggers numerous other downstream signaling pathways that affect endothelial cell survival, proliferation and blood vessel permeability [7].