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Titre du document / Document title

Effect of nitric oxide synthase inhibition on bleeding time in humans

Auteur(s) / Author(s)

SIMON D. I. ; STAMLER J. S. ; LOH E. ; LOSCALZO J. ; FRANCIS S. A. ; CREAGER M. A. ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

Boston univ. school medicine, Harvard medical school, cardiovascular pulmonary div., Boston MA 02115, ETATS-UNIS

Résumé / Abstract

Endothelium-derived nitric oxide (NO) is a potent in vitro inhibitor of platelet adhesion and aggregation, but its role in regulating platelet reactivity in vivo and in humans in particular is undefined. Our primary objective was to determine whether the in vivo inhibition of NO production shortens template bleeding time (BT). The hemodynamic and platelet effects of NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, were studied in 12 normal volunteers. Forearm template BT was determined before and 15 min after the intravenous (i.v.) infusion of 4.3 mg/kg L-NMMA. L-NMMA infusion increased mean arterial pressure from 88 ± 4 to 99 ± 3 mm Hg (p = 0.0001). Plasma NO levels, determined by chemiluminescence, decreased 65 ± 10% from basal values (p < 0.05), confirming inhibition of endogenous NO production. Intravenous L-NMMA shortened BT from 5.5 ± 0.9 to 4.0 ± 0.6 min (p = 0.026), or by 24 ± 8% (p = 0.008). L-NMMA infusion did not significantly change ex vivo platelet aggregation. To determine whether vasoconstriction affected BT, we investigated forearm blood flow (FBF ; determined by venous occlusion plethymography), and template BT in 3 subjects after the local infusion of L-NMMA (2-4 mg/min intraarterially, i.a.). Intraarterial administration of L-NMMA caused a 39 ± 3% (p = 0.006) reduction in FBF in the infused arm but did not change BT. These data show that systemic inhibition of NO production shortens BT in humans. However, the precise mechanism by which L-NMMA shortens BT is not completely defined.

Revue / Journal Title

Journal of cardiovascular pharmacology    ISSN  0160-2446   CODEN JCPCDT 

Source / Source

1995, vol. 26, no2, pp. 339-342 (13 ref.)

Langue / Language

Anglais

Editeur / Publisher

Lippincott, Hagerstown, MD, ETATS-UNIS  (1979) (Revue)

Mots-clés anglais / English Keywords

Enzyme inhibitor

;

Nitrogen monoxide

;

Nitric-oxide synthase

;

Normal

;

Human

;

Bleeding time

;

Platelet function

;

Gases

;

Oxidoreductases

;

Enzyme

;

Mots-clés français / French Keywords

Inhibiteur enzyme

;

Azote monoxyde

;

Nitric-oxide synthase

;

Normal

;

Homme

;

Temps saignement

;

Fonction thrombocytaire

;

Gaz

;

Oxidoreductases

;

Enzyme

;

Mots-clés espagnols / Spanish Keywords

Inhibidor enzima

;

Nitrógeno monóxido

;

Nitric-oxide synthase

;

Normal

;

Hombre

;

Tiempo sangrado

;

Función trombocitaria

;

Gas

;

Oxidoreductases

;

Enzima

;

Localisation / Location

INIST-CNRS, Cote INIST : 18065, 35400005361515.0210

Nº notice refdoc (ud4) : 3599831



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