Abstract | OBJECTIVE: METHODS: RESULTS: DS/H rats represented hypertension, left ventricular (LV) relaxation abnormality and myocardial stiffening with preserved systolic heart function. As compared with DS/L rats, DS/H rats showed higher levels of transforming growth factor-beta ( TGF-beta), connective tissue growth factor (CTGF), p22phox and gp91phox mRNA expression, NADPH oxidase activity and thiobarbituric acid-reactive substance ( TBARS) contents in LV tissues. Gene expression of uncoupling protein-2 (UCP-2), an inner mitochondrial membrane proton transporter, was also 2.8 +/- 0.5-fold higher. In DS/H rats, treatment with candesartan did not alter blood pressure, but resulted in a marked improvement of the hemodynamic deterioration; these therapeutic effects were accompanied by decreases in myocardial NADPH oxidase activity, TBARS contents and the expression of TGF-beta, CTGF, p22phox, gp91phox and UCP-2. Similar therapeutic effects were provided by treatment with tempol in DS/H rats. CONCLUSIONS: Our data suggest that NADPH oxidase-mediated ROS production contributes to the pathogenesis of DHF in DS hypertensive rats, and that the cardioprotective effects of AngII blockade are, at least partially, mediated through the suppression of this pathway.
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Authors | Peng Guo, Akira Nishiyama, Matlubur Rahman, Yukiko Nagai, Takahisa Noma, Tsunetatsu Namba, Makoto Ishizawa, Kazushi Murakami, Akira Miyatake, Shoji Kimura, Katsufumi Mizushige, Youichi Abe, Koji Ohmori, Masakazu Kohno |
Journal | Journal of hypertension
(J Hypertens)
Vol. 24
Issue 6
Pg. 1097-104
(Jun 2006)
ISSN: 0263-6352 [Print] England |
PMID | 16685210
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CCN2 protein, rat
- Immediate-Early Proteins
- Intercellular Signaling Peptides and Proteins
- Ion Channels
- Membrane Transport Proteins
- Mitochondrial Proteins
- Reactive Oxygen Species
- Thiobarbituric Acid Reactive Substances
- Transforming Growth Factor beta
- Ucp2 protein, rat
- Uncoupling Protein 2
- Angiotensin II
- Natriuretic Peptide, Brain
- Connective Tissue Growth Factor
- Collagen
- NADPH Oxidases
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Topics |
- Angiotensin II
(physiology)
- Animals
- Blood Pressure
(physiology)
- Collagen
(metabolism)
- Connective Tissue Growth Factor
- Diastole
(physiology)
- Gene Expression
- Heart Failure
(metabolism, pathology, physiopathology)
- Heart Ventricles
(metabolism, pathology)
- Hypertension
(physiopathology)
- Immediate-Early Proteins
(metabolism)
- Intercellular Signaling Peptides and Proteins
(metabolism)
- Ion Channels
- Lung
(pathology)
- Male
- Membrane Transport Proteins
(metabolism)
- Mitochondrial Proteins
(metabolism)
- Myocardium
(metabolism)
- NADPH Oxidases
(metabolism)
- Natriuretic Peptide, Brain
(metabolism)
- Organ Size
(physiology)
- Rats
- Rats, Inbred Dahl
- Reactive Oxygen Species
(metabolism)
- Thiobarbituric Acid Reactive Substances
(metabolism)
- Transforming Growth Factor beta
(metabolism)
- Uncoupling Protein 2
- Ventricular Dysfunction, Left
(metabolism, pathology, physiopathology)
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