title: The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems.
abstract: Despite increased pulsatile stress, thrombotic rather than hemorrhagic events represent a major complication of hypertension. The pathophysiology of thrombosis in hypertension involves the interaction among vascular endothelium and particularly the renin-angiotensin and kallikrein-kinin systems. Because hypertension is often associated with some degree of inflammation, the combination of chronic inflammation and chronic shear stress may convert the normal anticoagulant endothelium into a procoagulant surface, expressing tissue factor. Activation of the renin-angiotensin system leads to activation of nuclear factor kappaB-dependent proinflammatory genes, also accelerating the expression of tissue factor. Renin-angiotensin and kallikrein-kinin systems interact at several levels to modulate coagulation, fibrinolysis, and vasodilatation in such a way that these 2 systems could have a major influence on the occurrence of thrombotic complications. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists may favorably influence the balance between the renin-angiotensin and kallikrein-kinin axis, regulating blood pressure as well as reducing the risk of thrombosis, which may explain part of the clinical efficacy of these drugs.
authors.affiliation: Department of Medicine, University Hospital Maastricht, Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands.
authors.forename: Arne W J H
authors.initials: AW
authors.lastname: Dielis
authors.forename: Machiel
authors.initials: M
authors.lastname: Smid
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyak
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
mesh_terms: D000818:Animals; D001775:Blood Circulation; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D016234:Kallikrein-Kinin System; D012084:Renin-Angiotensin System; D013927:Thrombosis / Q000209:etiology*