The Prothrombotic Paradox of Hypertension: Role of the Renin-Angiotensin and Kallikrein-Kinin Systems

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2005-12, Vol.46 (6), p.1236-1242
• Main Authors: Dielis, Arne W.J.H, Smid, Machiel, Spronk, Henri M.H, Hamulyak, Karly, Kroon, Abraham A, ten Cate, Hugo, de Leeuw, Peter W
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Circulation; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Endocrine kidney. Renin-angiotensin-aldosterone system; Endothelium, Vascular - physiopathology; Experimental diseases; Fundamental and applied biological sciences. Psychology; Hemodynamics. Rheology; Humans; Hypertension - complications; Hypertension - physiopathology; Kallikrein-Kinin System; Medical sciences; Renin-Angiotensin System; Thrombosis - etiology; Vertebrates: cardiovascular system; Vertebrates: endocrinology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000193538.20705.23

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 κB–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.