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Title:
Angiotensin II InfusionāInduced Inflammation, Monocytic Fibroblast Precursor Infiltration, and Cardiac Fibrosis are Pressure Dependent | Cardiovascular Toxicology
Description:
The activated renināangiotensināaldosterone system increases blood pressure and intracellular signals, thus leading to cardiac fibrosis. Whether increased blood pressure or angiotensin II-activated signaling is responsible for elevated angiotensin IIāinduced cardiac remodeling is unknown. Here, we aimed to determine whether lowering blood pressure with hydralazine might prevent inflammation and cardiac fibrosis in response to angiotensin II. We used the C57/BL6 mouse model of angiotensin II infusion (1,500 ng/kg per minute) for 7 days; 40 male mice (6 weeks old) were randomly assigned to 4 groups for treatment: mice with angiotensin II or vehicle infusion were given hydralazine in drinking water (250 mg/l per day). Heart sections were stained with hematoxylin and eosin and Masson trichrome and examined by immunohistostaining. The levels of proinflammatory cytokines were measured by real-time PCR and western blot analysis. The blood pressure of the control group began to increase on day 4 of angiotensin II infusion, and hydralazine treatment prevented angiotensin IIāinduced hypertension. Compared with the control, hydralazine treatment to lower blood pressure blocked angiotensin IIāinduced fibrosis and reduced Mac-2+ inflammatory cell infiltration and proinflammatory cytokine expression. The accumulation of blood-borne CD45+ cells and α-smooth muscle actin-positive myofibroblasts was also significantly reduced. Our results indicate that elevated blood pressure is essential for inflammatory cell infiltration and myofibroblast formation, which contribute to angiotensin II infusionāinduced cardiac fibrosis. Hydralazine treatment attenuates cardiac fibrosis in response to angiotensin II. Lowering pressure could be an effective therapeutic target for cardiac fibrosis.
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- Cardiac angiotensin II: Does it have a function?
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headline:Angiotensin II InfusionāInduced Inflammation, Monocytic Fibroblast Precursor Infiltration, and Cardiac Fibrosis are Pressure Dependent
description:The activated renināangiotensināaldosterone system increases blood pressure and intracellular signals, thus leading to cardiac fibrosis. Whether increased blood pressure or angiotensin II-activated signaling is responsible for elevated angiotensin IIāinduced cardiac remodeling is unknown. Here, we aimed to determine whether lowering blood pressure with hydralazine might prevent inflammation and cardiac fibrosis in response to angiotensin II. We used the C57/BL6 mouse model of angiotensin II infusion (1,500Ā ng/kg per minute) for 7Ā days; 40 male mice (6Ā weeks old) were randomly assigned to 4 groups for treatment: mice with angiotensin II or vehicle infusion were given hydralazine in drinking water (250Ā mg/l per day). Heart sections were stained with hematoxylin and eosin and Masson trichrome and examined by immunohistostaining. The levels of proinflammatory cytokines were measured by real-time PCR and western blot analysis. The blood pressure of the control group began to increase on day 4 of angiotensin II infusion, and hydralazine treatment prevented angiotensin IIāinduced hypertension. Compared with the control, hydralazine treatment to lower blood pressure blocked angiotensin IIāinduced fibrosis and reduced Mac-2+ inflammatory cell infiltration and proinflammatory cytokine expression. The accumulation of blood-borne CD45+ cells and α-smooth muscle actin-positive myofibroblasts was also significantly reduced. Our results indicate that elevated blood pressure is essential for inflammatory cell infiltration and myofibroblast formation, which contribute to angiotensin II infusionāinduced cardiac fibrosis. Hydralazine treatment attenuates cardiac fibrosis in response to angiotensin II. Lowering pressure could be an effective therapeutic target for cardiac fibrosis.
datePublished:2011-03-04T00:00:00Z
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Inflammation
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Cardiac remodeling
Angiotensin II
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headline:Angiotensin II InfusionāInduced Inflammation, Monocytic Fibroblast Precursor Infiltration, and Cardiac Fibrosis are Pressure Dependent
description:The activated renināangiotensināaldosterone system increases blood pressure and intracellular signals, thus leading to cardiac fibrosis. Whether increased blood pressure or angiotensin II-activated signaling is responsible for elevated angiotensin IIāinduced cardiac remodeling is unknown. Here, we aimed to determine whether lowering blood pressure with hydralazine might prevent inflammation and cardiac fibrosis in response to angiotensin II. We used the C57/BL6 mouse model of angiotensin II infusion (1,500Ā ng/kg per minute) for 7Ā days; 40 male mice (6Ā weeks old) were randomly assigned to 4 groups for treatment: mice with angiotensin II or vehicle infusion were given hydralazine in drinking water (250Ā mg/l per day). Heart sections were stained with hematoxylin and eosin and Masson trichrome and examined by immunohistostaining. The levels of proinflammatory cytokines were measured by real-time PCR and western blot analysis. The blood pressure of the control group began to increase on day 4 of angiotensin II infusion, and hydralazine treatment prevented angiotensin IIāinduced hypertension. Compared with the control, hydralazine treatment to lower blood pressure blocked angiotensin IIāinduced fibrosis and reduced Mac-2+ inflammatory cell infiltration and proinflammatory cytokine expression. The accumulation of blood-borne CD45+ cells and α-smooth muscle actin-positive myofibroblasts was also significantly reduced. Our results indicate that elevated blood pressure is essential for inflammatory cell infiltration and myofibroblast formation, which contribute to angiotensin II infusionāinduced cardiac fibrosis. Hydralazine treatment attenuates cardiac fibrosis in response to angiotensin II. Lowering pressure could be an effective therapeutic target for cardiac fibrosis.
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Inflammation
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Cardiac remodeling
Angiotensin II
Pharmacology/Toxicology
Cardiology
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