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INHIBITORY EFFECTS OF ENDOGENOUS l ‐ARGININE ANALOGUES ON NITRIC OXIDE SYNTHESIS IN PLATELETS: ROLE IN PLATELET HYPERAGGREGABILITY IN HYPERTENSION
Author(s) -
De Meirelles Luisa R,
MendesRibeiro Antônio C,
Santoro Marcelle M,
Mendes Michely AP,
Da Silva Michele NSB,
Mann Giovanni E,
Brunini Tatiana MC
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04712.x
Subject(s) - platelet , arginine , nitric oxide , asymmetric dimethylarginine , endogeny , chemistry , medicine , endocrinology , nitric oxide synthase , platelet activation , fibrinogen , leucine , amino acid , biochemistry
SUMMARY1 An increase in plasma concentrations of endogenous l ‐arginine analogues, which are inhibitors of nitric oxide (NO) synthesis, may be involved in platelet activation and the increased risk of thrombosis in essential hypertension. Nitric oxide is synthesised in platelets from the amino acid l ‐arginine by inducible and constitutive isoforms of NO synthase (NOS), which leads to increased levels of cGMP. 2 In the present study, we investigated basal intraplatelet cGMP levels, platelet aggregation and pro‐inflammatory biomarkers in hypertensive patients. The effects of endogenous ( N G ‐monomethyl ‐l‐ arginine ( l ‐NMMA) and asymmetric dimethylarginine (ADMA); both at 1 mmol/L) and exogenous (aminoguanidine and N G ‐nitro‐ l ‐arginine; both at 1 mmol/L) l ‐arginine analogues and the neutral amino acid l ‐leucine (1 mmol/L) in inhibiting NOS activity in platelets were also investigated. 3 Twelve healthy controls and 18 hypertensive patients participated in the study. Platelet aggregation induced by collagen was increased in hypertensive patients (95 ± 5%) compared with controls (72 ± 5%). Basal NOS activity and intraplatelet cGMP levels were reduced in hypertensive platelets. Moreover, ADMA, l ‐NMMA and l ‐leucine were effective inhibitors of NO synthesis in both hypertensive and control platelets. Essential hypertension led to an inflammatory response, with increased plasma concentrations of fibrinogen, C‐reactive protein and cytokines. 4 These findings provide evidence that, in essential arterial hypertension, the enhanced plasma levels of endogenous l ‐arginine analogues ADMA and l ‐NMMA, potent inhibitors of l ‐arginine transport and NO synthesis in platelets, may play a role in increased platelet aggregation via a cGMP‐dependent mechanism.