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Compensatory mechanisms influence hemostasis in setting of eNOS deficiency
- Source :
- American journal of physiology. Heart and circulatory physiology. 288(4)
- Publication Year :
- 2004
-
Abstract
- The balance between thrombosis and hemorrhage is carefully regulated. Nitric oxide (NO) is an important mediator of these processes, as it prevents platelet adhesion to the endothelium and inhibits platelet recruitment. Although endothelial NO synthase (eNOS)-deficient mice have decreased vascular reactivity and mild hypertension, enhanced thrombosis in vivo has not been demonstrated. To determine the role of endogenous NO in hemostasis, a model of carotid arterial injury and thrombosis was performed using eNOS-deficient and wild-type mice. Paradoxically, the eNOS-deficient animals had a prolongation of time to occlusion compared with the wild-type mice ( P < 0.001). Consistent with this finding, plasma markers suggesting enhanced fibrinolysis [tissue plasminogen activator (t-PA) activity and antigen and D-dimer levels] were significantly elevated in eNOS-deficient animals. Vascular tissue expression of t-PA and platelet activity levels were not altered. In endothelial cells, t-PA is stored in Weibel-Palade bodies, and exocytosis of these storage granules is inhibited by NO. Thus in the absence of NO, release of Weibel-Palade body contents (and t-PA) could be enhanced; this observation is also supported by increased von Willebrand factor levels observed in eNOS-deficient animals. In summary, although eNOS deficiency attenuates vascular reactivity and increases platelet recruitment, it is also associated with enhanced fibrinolysis due to lack of NO-dependent inhibition of Weibel-Palade body release. These processes highlight the complexity of NO-dependent regulation of vascular homeostasis. Such compensatory mechanisms may partially explain the lack of spontaneous thrombosis, minimally elevated baseline blood pressure, and normal life span that are seen in animals deficient in a pivotal regulator of vascular patency.
- Subjects :
- Male
medicine.medical_specialty
Endothelium
Nitric Oxide Synthase Type III
Physiology
Nitric Oxide Synthase Type II
Mice, Transgenic
Nitric Oxide
Nitric oxide
chemistry.chemical_compound
Mice
Mediator
Enos
Physiology (medical)
Internal medicine
von Willebrand Factor
medicine
Animals
Platelet
Hemostasis
biology
Weibel-Palade Bodies
Fibrinolysis
medicine.disease
biology.organism_classification
Platelet Activation
Thrombosis
Nitric oxide synthase
Disease Models, Animal
P-Selectin
medicine.anatomical_structure
Endocrinology
chemistry
Tissue Plasminogen Activator
Immunology
biology.protein
Female
Nitric Oxide Synthase
Cardiology and Cardiovascular Medicine
Carotid Artery Injuries
Subjects
Details
- ISSN :
- 03636135
- Volume :
- 288
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Accession number :
- edsair.doi.dedup.....e7d2a9b8b42644e6c9036282b49f9e6f