The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems.
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.
Dielis
Arne W J H
AW
Department of Medicine, University Hospital Maastricht, Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands.
Smid
Machiel
M
Spronk
Henri M H
HM
Hamulyak
Karly
K
Kroon
Abraham A
AA
ten Cate
Hugo
H
de Leeuw
Peter W
PW
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*