title: Pathogenesis and treatment of the cardiorenal syndrome: Implications of L-arginine-nitric oxide pathway impairment.
abstract: A highly complex interplay exists between the heart and kidney in the setting of both normal and abnormal physiology. In the context of heart failure, a pathophysiological condition termed the cardiorenal syndrome (CRS) exists whereby dysfunction in the heart or kidney can accelerate pathology in the other organ. The mechanisms that underpin CRS are complex, and include neuro-hormonal activation, oxidative stress and endothelial dysfunction. The endothelium plays a central role in the regulation of both cardiac and renal function, and as such impairments in endothelial function can lead to dysfunction of both these organs. In particular, reduced bioavailability of nitric oxide (NO) is a key pathophysiologic component of endothelial dysfunction. The synthesis of NO by the endothelium is critically dependent on the plasmalemmal transport of its substrate, L-arginine, via the cationic amino acid transporter-1 (CAT1). Impaired L-arginine-NO pathway activity has been demonstrated individually in heart and renal failure. Recent findings suggest abnormalities of the L-arginine-NO pathway also play a role in the pathogenesis of CRS and thus this pathway may represent a potential new target for the treatment of heart and renal failure.
authors.affiliation: Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Physiology, Monash University, Melbourne, Australia. Electronic address: niwanthi.rajapakse@bakeridi.edu.au.
authors.forename: Niwanthi W
authors.initials: NW
authors.lastname: Rajapakse
authors.affiliation: Department of Medicine, Monash University, Melbourne Australia.
authors.forename: Shane
authors.initials: S
authors.lastname: Nanayakkara
authors.affiliation: Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Department of Medicine, Monash University, Melbourne Australia; Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D059347:Cardio-Renal Syndrome / Q000145:classification / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D002317:Cardiovascular Agents / Q000627:therapeutic use; D027201:Cationic Amino Acid Transporter 1 / Q000378:metabolism; D004232:Diuretics / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000378:metabolism*; D004921:Erythropoietin / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D013564:Sympathetic Nervous System / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002317:Cardiovascular Agents; D027201:Cationic Amino Acid Transporter 1; D004232:Diuretics; D018836:Inflammation Mediators; D004921:Erythropoietin; D009569:Nitric Oxide; D001120:Arginine
keywords: Endothelium; Heart; Kidney; L-arginine transporters; Nitric oxide; Oxidative stress