Adrenomedullin: a cardiac depressant factor in septic shock

Despite intensive research, septic shock is still the most common cause of death in surgical intensive care, and its incidence keeps increasing. No curative treatment is yet available. The critical aspect of septic shock is the refractory hypotension that develops during its late phase which leads to a progressive deterioration of cell and organ functions, and in most instances, death. During septic shock, following the overproduction of cytokines, many factors such as nitric oxide and adrenomedullin (ADM) are produced in abnormally large quantities, but our understanding of their contribution to the pathophysiology of sepsis is limited. Here we show that adrenomedullin (22-52), an adrenomedullin receptor antagonist, improves the contractility of myocytes isolated from lipopolysaccharide (LPS)-treated rats, whereas in normal myocytes, adrenomedullin, acting through an adrenomedullin (22-52) sensitive receptor, decreases their contractility. In addition, adrenomedullin antiserum and inducible nitric oxide (NO) synthase inhibitor improve the survival of LPS-treated rats. The data indicate that adrenomedullin is a cardiac depressant factor, which along with NO precipitates ventricular failure during septic shock.