Tissue Angiotensin II Generating System by Angiotensin-Converting Enzyme and Chymase

Miyazaki, Mizuo; Takai, Shinji

doi:10.1254/jphs.cpj06008x

Cited by 101 publications

(66 citation statements)

References 35 publications

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“…We demonstrated that captopril treatment significantly inhibits the expression and activity of MMP-9 and the expression of MMP-2. It has not also been clarified whether ACE inhibitors directly affect the heart or indirectly influence it by improving hemodynamics in cardiac disease (31). In the present study, captopril attenuated monocrotaline-induced cardiac hypertrophy without affecting pulmonary artery pressure.…”

Section: Discussionmentioning

confidence: 47%

Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats

et al. 2008

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Abstract. Little is known about the influence of angiotensin converting enzyme (ACE) inhibitors on matrix metalloproteinase (MMP) in right ventricular remodeling. We investigated the effect of captopril, an ACE inhibitor, on MMP-2 and MMP-9 in monocrotaline-induced right ventricular hypertrophy. Six-week-old male Wistar rats were injected intraperitoneally with monocrotaline (60 mg/ kg) or saline. The rats were administrated captopril (30 mg / kg per day) or a vehicle orally for 24 days from the day of monocrotaline injection. At day 25, echocardiography was performed and hearts were excised. Expressions and activities of MMP-2 and MMP-9 were measured by Western blotting and by gelatin zymography, respectively. In monocrotalineinjected rats, right ventricular weight / tail length ratio increased significantly. Histological analysis revealed cardiomyocyte hypertrophy and fibrosis in right ventricular sections. Echocardiography showed right ventricular dysfunction compared with saline-injected rats. The right ventricular hypertrophy, fibrosis, and dysfunction were inhibited by captopril. However, captopril did not attenuate an increase in pulmonary artery pressure. MMP-2 and MMP-9 expressions and activities in right ventricles increased significantly in monocrotaline-injected rats and captopril inhibited them. These findings indicate that captopril attenuates the development of monocrotalineinduced right ventricular hypertrophy in association with inhibition of MMP-2 and MMP-9 in rats.

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Section: Discussionmentioning

confidence: 47%

Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats

et al. 2008

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“…The mechanism by which mast cell degranulation activates the RAS is not clear. Possible pathways of activation include mast cell AngI-converting chymase (15)(16)(17), or release of renin, which has been demonstrated in myocardial mast cells (18,19).…”

Section: Studies In the Mesenteric Microcirculationmentioning

confidence: 99%

The Systemic Inflammation of Alveolar Hypoxia Is Initiated by Alveolar Macrophage–Borne Mediator(s)

Chao

Wood²,

Blanco³

et al. 2009

Am J Respir Cell Mol Biol

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Alveolar hypoxia produces widespread systemic inflammation in rats. The inflammation appears to be triggered by activation of mast cells by a mediator released from alveolar macrophages, not by the reduced systemic partial pressure of oxygen (PO 2 ). If this is correct, the following should apply: (1) neither mast cells nor tissue macrophages should be directly activated by hypoxia; and (2) mast cells should be activated when in contact with hypoxic alveolar macrophages, but not with hypoxic tissue macrophages. We sought here to determine whether hypoxia activates isolated alveolar macrophages, peritoneal macrophages, and peritoneal mast cells, and to study the response of the microcirculation to supernatants of these cultures. Rat mesenteric microcirculation intravital microscopy was combined with primary cultures of alveolar macrophages, peritoneal macrophages, and peritoneal mast cells. Supernatant of hypoxic alveolar macrophages, but not of hypoxic peritoneal macrophages, produced inflammation in mesentery. Hypoxia induced a respiratory burst in alveolar, but not peritoneal macrophages. Cultured peritoneal mast cells did not degranulate with hypoxia. Immersion of mast cells in supernatant of hypoxic alveolar macrophages, but not in supernatant of hypoxic peritoneal macrophages, induced mast cell degranulation. Hypoxia induced release of monocyte chemoattractant protein-1, a mast cell secretagogue, from alveolar, but not peritoneal macrophages or mast cells. We conclude that a mediator released by hypoxic alveolar macrophages activates mast cells and triggers systemic inflammation. Reduced systemic PO 2 and activation of tissue macrophages do not play a role in this phenomenon. The inflammation could contribute to systemic effects of diseases featuring alveolar hypoxia.Keywords: hypoxia; systemic inflammation; alveolar macrophages; mast cells; monocyte chemoattractant protein Alveolar hypoxia, induced by reduction of inspired PO 2 , initiates a rapid and widespread inflammatory response in mesentery (1), skeletal muscle (2, 3), and brain (4) of rats. The inflammation is characterized by increased microvascular levels of reactive oxygen species (ROS) (5), perivascular mast cell degranulation (2, 3, 6), increased leukocyte-endothelial adhesive interactions (1), and extravasation of albumin (7).Studies in the cremaster microcirculation suggest that the inflammation elicited by alveolar hypoxia is not triggered by the reduction of cremaster PO 2 , but rather by a mediator released from a distant site and transported by the circulation. This idea is supported by two lines of evidence: first, selective reduction of cremaster PO 2 does not produce mast cell degranulation and inflammation in the cremaster microcirculation unless alveolar PO 2 is also reduced (2, 3); second, plasma obtained from hypoxic rats applied to the normoxic cremaster produces an inflammatory response similar to that elicited by alveolar hypoxia (8). The response to hypoxic rat plasma is not due to inflammatory mediators released into plasma by...

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“…Since, chymase is kept in control by AAT [21], it is quite possible that overexpression of chymase triggers the up-regulation of AAT in VKC patients. Chymase converts angiotensin-I to angiotensin-II [22] and also activates some endogenous peptides like endothelin, stem cell factor and interleukin-1β (IL-1β) [23], IL-1, IL-6, TNF-α and lipopolysaccharides have shown to up-regulate the synthesis of AAT [24]. IL-1 may therefore account for the increased antitryptic activity in the serum of VKC patients.…”

Section: Discussionmentioning

confidence: 99%

Alpha-1 Antitrypsin, a Diagnostic and Prognostic Marker of Vernal Keratoconjunctivitis

Ahsan

Salman

Alam

et al. 2014

JCDR

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Tissue Angiotensin II Generating System by Angiotensin-Converting Enzyme and Chymase

Cited by 101 publications

References 35 publications

Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats

Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats

The Systemic Inflammation of Alveolar Hypoxia Is Initiated by Alveolar Macrophage–Borne Mediator(s)

Alpha-1 Antitrypsin, a Diagnostic and Prognostic Marker of Vernal Keratoconjunctivitis

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