Natriuretic peptides and the management of heart failure.
Hyperactivation of the renin-angiotensin-aldosterone system (RAAS), heightened sympathetic drive and uncontrolled synthesis of inflammatory cytokines, exacerbates ventricular contractile dysfunction in heart failure patients. The pathophysiological consequences include excessive fluid retention, increased peripheral vascular resistance, and endothelial dysfunction. Consequently, the demand for additional work by the failing myocardium in the presence of a greater afterload cannot be sustained. Therapeutically exploiting the natriuretic peptide system may represent a physiological approach to dampen the deleterious effects of the neuroendocrine systems and inflammatory cytokines. In both patients and animal models of heart failure, pharmacologically increasing plasma natriuretic peptide levels ameliorated vascular tone, renal and endothelial function, and ventricular contractility. Based on these observations, the following review will highlight the therapeutic benefits of the natriuretic peptide system in heart failure.
Montreal Heart Institute, Department of Physiology, University of Montreal, Montreal, Quebec, Canada. calderon@icm.umontreal.ca
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Calderone
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D014409:Tumor Necrosis Factor-alpha; D009320:Atrial Natriuretic Factor; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III