Inhibition of l-arginine transport in platelets by asymmetric dimethylarginine and N-monomethyl-l-arginine: effects of arterial hypertension.
Clin Exp Pharmacol Physiol
; 31(10): 738-40, 2004 Oct.
Article
en En
| MEDLINE
| ID: mdl-15554917
ABSTRACT
Nitric oxide (NO) produced by human platelets plays an important role in all stages of platelet activation. l-Arginine, the precursor for NO synthesis, modulates NO production by platelets. The l-arginine analogues asymmetric dimethylarginine (ADMA) and N(G)-monomethyl-l-arginine (l-NMMA) are endogenous inhibitors of nitric oxide synthase (NOS), involved in the physiopathology of arterial hypertension. The aim of the present study was to investigate the inhibitory effects of endogenous and exogenous l-arginine analogues on l-arginine influx in platelets from healthy controls and hypertensive patients. Twelve patients with uncomplicated essential hypertension (stage I) and 15 age-matched normotensive controls participated in the present study. Platelets were isolated and incubated with l-[(3)H]-arginine and increasing concentrations of l-arginine analogues (5-2000 micromol/L). The influx of l-arginine was inhibited in a concentration-dependent manner by l-NMMA in platelets from controls (K(i) = 42 +/- 6 micromol/L) and this inhibitory effect was markedly higher in hypertensive platelets (K(i) = 23 +/- 4 micromol/L). Similarly, the K(i) for ADMA inhibition of l-arginine transport was significantly more pronounced in platelets from hypertensive patients (K(i) = 16 +/- 1 micromol/L) compared with controls (K(i) = 27 +/- 2 micromol/L). In contrast, N(G)-nitro-l-arginine methyl ester (l-NAME) was found to be a weak inhibitor of l-arginine influx in platelets from controls (K(i) = 1917 +/- 319 micromol/L) and hypertensive patients (K(i) = 2279 +/- 578 micromol/L). Aminoguanidine, a selective inhibitor of inducible NOS, failed to inhibit l-arginine transport. Our findings provide the first evidence that ADMA and l-NMMA markedly inhibit l-arginine transport in human platelets, an effect that is more pronounced in hypertensive patients. It is possible that endogenous l-arginine analogues, by inhibiting NO synthesis, are involved in the platelet activation present in hypertension.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Arginina
/
Plaquetas
/
Óxido Nítrico Sintasa
/
Omega-N-Metilarginina
/
Inhibidores Enzimáticos
/
Hipertensión
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Exp Pharmacol Physiol
Año:
2004
Tipo del documento:
Article
País de afiliación:
Brasil