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Hemostasis imbalance in experimental hypertension
Delphine Corseaux1, Véronique Ollivier, Vincent Fontaine
1INSERM U479, Faculté Xavier Bichat, Paris, France.
Molecular Medicine (Cambridge, Mass.)
|August 1, 2002
Summary
Chronic nitric oxide inhibition in rats promotes thrombin generation and impairs fibrinolysis, contributing to thrombotic complications in hypertension. Treatment with an ACE inhibitor prevented these effects.
Area of Science:
- Cardiovascular Research
- Nephrology
- Hematology
Background:
- N(G)-nitro-L-arginine methyl ester (L-NAME) in rats causes hypertension and ischemic damage.
- The molecular mechanisms of L-NAME-induced thrombosis require elucidation.
Purpose of the Study:
- To investigate the molecular basis of thrombotic events in L-NAME-induced hypertension.
- To assess the impact of L-NAME on coagulation and fibrinolysis.
Main Methods:
- Measurement of plasma thrombin generation markers (thrombin-antithrombin complexes, soluble glycoprotein V) via ELISA.
- Assessment of platelet aggregation ex vivo.
- Quantification of tissue factor mRNA and activity in aortic and renal tissues.
- Evaluation of fibrinolytic system components, including plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) activity.
Main Results:
- L-NAME increased thrombin generation markers and impaired platelet aggregation.
- Tissue factor expression and activity were elevated in aortic and renal arterioles.
- The fibrinolytic system was compromised, with increased plasma PAI-1 and arterial PAI-1 mRNA.
- Hypertensive arterial walls showed increased antifibrinolytic activity and t-PA complexation.
Conclusions:
- Chronic nitric oxide blockade enhances thrombin generation and tissue factor activity.
- Impaired vascular fibrinolysis contributes to thrombotic complications in hypertension.
- Angiotensin-converting enzyme (ACE) inhibition with Zofenil normalized these pro-thrombotic parameters.