Nitric oxide, malnutrition and chronic renal failure.
The conditionally essential amino acid L-arginine is the substrate for nitric oxide (NO) synthesis, a key second messenger involved in physiological functions including endothelium-dependent vascular relaxation and inhibition of platelet adhesion and aggregation. Extracellular L-arginine transport seems to be essential for the production of NO by the action of NO synthases (NOS), even when the intracellular levels of L-arginine are available in excess (L-arginine paradox). Chronic renal failure (CRF) is a complex clinical condition associated with accelerated atherosclerosis and thrombosis leading to cardiovascular events. Various studies document that markers of malnutrition and inflammation, such as low body mass index (BMI), C-reactive protein (CRP) and interleukin-6 (IL-6), are strong independent predictors of cardiovascular mortality in patients with end-stage renal disease (ESRD). There is considerable literature demonstrating that a disturbance in the nitric oxide control mechanism plays a role in mediating the haemodynamic and haemostatic disorders present in CRF. Endogenous analogues of L-arginine, ADMA and L-NMMA, which can inhibit NO synthesis and L-arginine transport, are increased whilst L-arginine is reduced in plasma from all stages of CRF patients. In this context, the uptake of L-arginine in blood cells is increased in undialysed CRF patients and in patients treated by CAPD and haemodialysis. In platelets obtained from haemodialysis patients, the activation of L-arginine transport and NO production was limited to well-nourished patients. Impairment in nitric oxide bioactivity, coupled with malnutrition and inflammation, may contribute to increased incidence of atherothrombotic events in CRF. This article summarizes the current knowledge of L-arginine-nitric oxide pathway and malnutrition in CRF and briefly describes possible therapeutic interventions.
Brunini
Tatiana M C
TM
Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Moss
Monique B
MB
Siqueira
Mariana A S
MA
Santos
Sérgio F F
SF
Lugon
Jocemir R
JR
Mendes-Ribeiro
Antônio C
AC
D001120:Arginine / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000188:drug therapy*; D044342:Malnutrition / Q000150:complications*; D009569:Nitric Oxide / Q000378:metabolism*
D009569:Nitric Oxide; D001120:Arginine