Journal article
Angiotensin II-mediated microvascular thrombosis
Hypertension (Dallas, Tex. 1979), Vol.56(6), pp.1089-1095
12/2010
Handle:
https://hdl.handle.net/2376/108954
PMCID: PMC3023299
PMID: 20975035
Abstract
Hypertension is associated with an increased risk of thrombosis that appears to involve an interaction between the renin-angiotensin system and hemostasis. In this study we determined whether angiotensin II-mediatedthrombosis occurs in arterioles and/or venules, and assessed the involvement of type-1 (AT1), type-2 (AT2) and type 4 (AT4) angiotensin II receptors, as well as receptors for endothelin-1 (ET-1) and bradykinin (BK-1, BK-2) in angiotensin II-enhanced microvascular thrombosis. Thrombus development in mouse cremaster microvessels was quantified after light/dye injury using the time of onset of the thrombus and time to blood flow cessation. Wild type and AT1-receptor deficient mice were implanted with an angiotensin II-loaded Alzet pump for 2 wks. Angiotensin II administration in both wild type and AT1-receptor deficient mice significantly accelerated thrombosis in arterioles. Genetic deficiency and pharmacological antagonism of AT1-receptors did not alter the thrombosis response to angiotensin II. Isolated murine platelets aggregated in response to low (pM), but not high (nM), concentrations of angiotensin II. The platelet aggregation response to angiotensin II was dependent on AT1-receptors. Antagonism of AT2-receptors
in vivo
significantly prolonged the onset of angiotensin II enhanced thrombosis, while an AT4-receptor antagonist prolonged the time to flow cessation. Selective antagonism of either ET-1 or BK-1 receptors largely prevented both the onset and flow cessation responses to chronic angiotensin II infusion. Our findings indicate that angiotensin II-induced hypertension is accompanied by enhanced thrombosis in arterioles and this response is mediated by a mechanism that involves AT2, AT4, BK-1 and ET-1 receptor-mediated signaling.
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Details
- Title
- Angiotensin II-mediated microvascular thrombosis
- Creators
- Elena Y Senchenkova - Department of Molecular & Cellular Physiology, LSU Health Sciences Center, Shreveport 71130-3932Janice Russell - Department of Molecular & Cellular Physiology, LSU Health Sciences Center, Shreveport 71130-3932Lidiana D Almeida-Paula - Department of Molecular & Cellular Physiology, LSU Health Sciences Center, Shreveport 71130-3932Joseph W Harding - Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WashingtonD. Neil Granger - Department of Molecular & Cellular Physiology, LSU Health Sciences Center, Shreveport 71130-3932
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.56(6), pp.1089-1095
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Identifiers
- 99900547494401842
- Language
- English
- Resource Type
- Journal article