title: Hemostasis imbalance in experimental hypertension.
abstract: BACKGROUND
  The rat model of chronic intoxication by N(G) -nitro-L-arginine methyl ester (L-NAME) induces severe systemic arterial hypertension and progressive ischemic lesions in the central nervous system and kidneys. We investigated the possible molecular basis of these thrombotic events.
  
  
  RESULTS
  Administration of L-NAME increased plasma markers of thrombin generation, thrombin-antithrombin complexes, and soluble glycoprotein V, measured by specific ELISA. Thrombin generation in vivo was associated with ex vivo platelet desensitization to adenosine 5'-diphosphate and collagen-induced aggregation. In the aortic layers and renal arterioles, tissue factor mRNA (semi-quantitative RT-PCR) and activity (coagulation assay) were increased. In contrast, tissue factor activity was not modified in glomeruli. In parallel, an impairment of the fibrinolytic system was demonstrated by an increase in plasma levels and arterial secretion of plasminogen activator inhibitor-1. In the arterial wall, plasminogen activator inhibtor-1 mRNA was significantly increased. Moreover, antifibrinolytic activity, studied by fibrin reverse zymography, was increased whereas all tissue-plasminogen activator activity secreted by the hypertensive arterial wall was detected as complexes with its specific inhibitor. In animals treated with the angiotensin-converting enzyme (ACE) inhibitor Zofenil, all of these parameters remained at control levels.
  
  
  CONCLUSIONS
  These results indicate that chronic blockade of nitric oxide production in rats results in enhancement of blood markers of thrombin generation associated with tissue factor induction and impairment of fibrinolysis in the vascular wall, which may contribute to the thrombotic complications associated with hypertension.
authors.affiliation: INSERM U479, Faculté Xavier Bichat, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Corseaux
authors.forename: Véronique
authors.initials: V
authors.lastname: Ollivier
authors.forename: Vincent
authors.initials: V
authors.lastname: Fontaine
authors.forename: Marie-Geneviève
authors.initials: MG
authors.lastname: Huisse
authors.forename: Monique
authors.initials: M
authors.lastname: Philippe
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.forename: Roger
authors.initials: R
authors.lastname: Vranckx
authors.forename: Catherine
authors.initials: C
authors.lastname: Ravanat
authors.forename: François
authors.initials: F
authors.lastname: Lanza
authors.forename: Edouardo
authors.initials: E
authors.lastname: Angles-Cano
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guillin
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000378:metabolism; D001158:Arteries / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology; D006487:Hemostasis / Q000502:physiology*; D006973:Hypertension / Q000097:blood* / Q000139:chemically induced; D007678:Kidney Glomerulus / Q000033:anatomy & histology / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009929:Organ Size; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D019331:NG-Nitroarginine Methyl Ester