The role of exercise on L-arginine nitric oxide pathway in chronic heart failure.

Chronic heart failure (CHF) is a pathological state with high morbidity and mortality and the full understanding of its genesis remain to be elucidated. In this syndrome, a cascade of neurohormonal and hemodynamic mechanisms, as well as inflammatory mediators, are activated to improve the impaired cardiac function. Clinical and experimental observations have shown that CHF is associated with a generalized disturbance in endothelium-dependent vasodilation, which may contribute to the progression of ventricular and vascular remodelling in this syndrome. There is also accumulating evidence that disturbances in nitric oxide (NO) availability is involved in the development of heart failure at the systemic and cardiac levels. NO is a ubiquitous signalling molecule which causes potent vasodilation, inhibits platelet activation and regulates the contractile properties of cardiac myocytes. It is generated from the amino acid L-arginine via constitutive and inducible isoforms of the enzyme NO synthase (NOS). There is evidence that exercise, a nonpharmacological tool, improves symptoms, fitness (VO(2peak)), quality of life and NO bioavailability in CHF population. This review examines different aspects of the L-arginine-NO pathway and inflammation in the physiopathology of CHF and highlights the important beneficial effects of exercise in this disease.

Characterization of cationic amino acid transport systems in rat erythrocytes: lack of effect of uraemia on L-arginine influx.

1. Chronic renal failure (CRF) is associated with the abnormal regulation of nitric oxide (NO) synthesis at the systemic level. The transport of L-arginine, upregulated in blood cells from uraemic patients, modulates NO synthesis in this pathological condition. The model of partial nephrectomy in rats is widely accepted as a valid model of uraemia. Because there are no reports of L-arginine transport in blood cells from uraemic rats, the aim of the present study was to investigate L-arginine transport in red blood cells (RBCs) from these rats. 2. The kinetics of L-arginine transport in RBC and plasma and the amino acid profiles of RBC were investigated in control, sham-operated and subtotally nephrectomized rats. 3. L-Arginine transport was mediated via the cationic amino acid transport system y+ and a transport system with kinetics resembling the human system y+L. In control RBC, the apparent Ki for L-leucine inhibition of L-arginine transport via system y+L was 0.16 +/- 0.02 and 4.8 +/- 2 mmol/L in the presence of Li+ and Na+, respectively. 4. The Vmax values for L-arginine transport via system y+L and system y+ were similar in RBC from control sham-operated and uraemic rats. Moreover, L-arginine concentrations in plasma and RBC were not affected by uraemia. 5. The findings of the present study provide the first evidence that L-arginine transport in rat erythrocytes is mediated by two distinct cationic transport systems with characteristics of systems y+ and y+L, which accept neutral amino acids only in the presence of Li+. In contrast with previous studies in uraemic patients, plasma levels and maximal transport rates of L-arginine were not altered in this rat model of CRF.