THE ROLE OF NITRIC-OXIDE AND CYTOKINES IN HEART-FAILURE

Heart failure is a common problem associated with considerable mortali ty and morbidity, The mechanisms underlying the heart failure syndrome , which remain poorly understood, may involve an inflammatory process. Nitric oxide (NO) and various cytokines could play an important role in this inflammatory process. Recent evidence has emerged in both anim al models and humans suggesting that both of these mediators may play an important role in heart failure. NO is synthesized by the NO syntha se family of enzymes, Two of these enzymes are constitutive, endotheli al NO synthase and neuronal NO synthase. The third enzyme, inducible N O synthase, is capable of producing large amounts of NO once induced b y mediators such as interleukin (IL)-1, IL-2, IL-6, tumour necrosis fa ctor (TNF)-alpha, and interferon-gamma. Endothelial NO synthase is pre sent in the heart in the endocardium, cardiac myocytes, and cardiac co nduction tissue, Inducible NO synthase is present in cardiac myocytes, endocardium, vascular smooth muscle cells, and infiltrating inflammat ory cells. Evidence from both animal models and patients suggests that NO exerts a negative inotropic effect, Increased inducible NO synthas e, TNF-alpha, and IL-6 have been found in patients with heart failure in several studies, In other studies, decreased endothelial NO synthas e was found in patients with heart failure. TNF-alpha and IL-6 may be produced in heart failure and may induce inducible NO synthase, result ing in NO production, which acts as a negative inotrope. Endothelial N O synthase may be decreased as a result of downregulation by TNF-alpha inducible NO synthase. The possible role of these mediators in heart failure needs further evaluation because these findings could have nov el therapeutic implications. (C) Rapid Science Publishers.