INHIBITORY EFFECTS OF ENDOGENOUS l-ARGININE ANALOGUES ON NITRIC OXIDE SYNTHESIS IN PLATELETS: ROLE IN PLATELET HYPERAGGREGABILITY IN HYPERTENSION

  1. Luisa R De Meirelles1,
  2. Antônio C Mendes-Ribeiro1,2,
  3. Marcelle M Santoro1,
  4. Michely AP Mendes1,
  5. Michele NSB Da Silva1,
  6. Giovanni E Mann3,
  7. Tatiana MC Brunini1

Article first published online: 9 JUL 2007

DOI: 10.1111/j.1440-1681.2007.04712.x

Issue

Clinical and Experimental Pharmacology and Physiology

Clinical and Experimental Pharmacology and Physiology

Volume 34, Issue 12, pages 1267–1271, December 2007

Additional Information

How to Cite

De Meirelles, L. R., Mendes-Ribeiro, A. C., Santoro, M. M., Mendes, M. A., Da Silva, M. N., Mann, G. E. and Brunini, T. M. (2007), INHIBITORY EFFECTS OF ENDOGENOUS l-ARGININE ANALOGUES ON NITRIC OXIDE SYNTHESIS IN PLATELETS: ROLE IN PLATELET HYPERAGGREGABILITY IN HYPERTENSION. Clinical and Experimental Pharmacology and Physiology, 34: 1267–1271. doi: 10.1111/j.1440-1681.2007.04712.x

Author Information

  1. 1

    Pharmacology Department, State University of Rio de Janeiro,

  2. 2

    Discipline of Pharmacology, Department of Physiological Sciences, UNIRIO, Rio de Janeiro, Brazil and

  3. 3

    Cardiovascular Division, School of Biomedical and Health Sciences, King's College London, London, UK

* Dr Tatiana Marlowe Cunha Brunini, Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 20551-030, Brazil. Email: tmcbrunini@yahoo.com.br

Publication History

  1. Issue published online: 15 AUG 2007
  2. Article first published online: 9 JUL 2007
  3. Received 13 January 2007; revision 2 May 2007; accepted 4 May 2007.

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Keywords:

  • asymmetric dimethylarginine;
  • hypertension;
  • NG-monomethyl-l-arginine;
  • nitric oxide;
  • platelets

SUMMARY

  • 1
    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 (NG-monomethyl-l-arginine (l-NMMA) and asymmetric dimethylarginine (ADMA); both at 1 mmol/L) and exogenous (aminoguanidine and NG-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.
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