Chymase plays an important role in left ventricular remodeling induced by intermittent hypoxia in mice.

Abstract

Intermittent hypoxia caused by sleep apnea is associated with cardiovascular disease. Chymase has been reported to play an important role in the development of cardiovascular disease, but it is unclear whether chymase is involved in the pathogenesis of left ventricular remodeling induced by intermittent hypoxia. The aim of this study was to evaluate the effect of a novel chymase inhibitor (NK3201) on hypoxia-induced left ventricular remodeling in mice. Male C57BL/6J mice (9 weeks old) were exposed to intermittent hypoxia or normoxia and were treated with NK3201 (10 mg/kg per day) or the vehicle for 10 days. Left ventricular systolic pressure showed no significant differences among all of the experimental groups. Exposure to intermittent hypoxia increased left ventricular chymase activity and angiotensin II expression, which were both suppressed by treatment with NK3201. Intermittent hypoxia also increased the mean cardiomyocyte diameter, perivascular fibrosis, expression of inflammatory cytokines, oxidative stress, and NADPH-dependent superoxide production in the left ventricular myocardium. These changes were all suppressed by NK3201 treatment. Therefore, chymase might play an important role in intermittent hypoxia-induced left ventricular remodeling, which is independent of the systemic blood pressure.

• Authors: Chika Matsumoto, Tetsuya Hayashi, Kento Kitada, Chika Yamashita, Masatoshi Miyamura, Tatsuhiko Mori, Akira Ukimura, Mamoru Ohkita, Denan Jin, Shinji Takai, Mizuo Miyazaki, Yoshikatsu Okada, Yasushi Kitaura, Yasuo Matsumura
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 54 Issue 1 Pg. 164-71 (Jul 2009) ISSN: 1524-4563 [Electronic] United States
• PMID: 19470876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetamides
• Aldehydes
• Interleukin-6
• Lipid Peroxides
• NK3201
• Pyrimidines
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha
• Superoxides
• Angiotensin II
• NADP
• Chymases
• 4-hydroxy-2-nonenal

Topics

• Acetamides (pharmacology)
• Aldehydes (metabolism)
• Angiotensin II (metabolism)
• Animals
• Body Weight
• Chymases (antagonists & inhibitors, metabolism)
• Gene Expression (drug effects)
• Hemodynamics (drug effects, physiology)
• Hypoxia (physiopathology)
• Immunohistochemistry
• Interleukin-6 (genetics)
• Lipid Peroxides (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism)
• NADP (metabolism)
• Organ Size
• Pyrimidines (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Superoxides (metabolism)
• Transforming Growth Factor beta (genetics)
• Tumor Necrosis Factor-alpha (genetics)
• Ventricular Remodeling (drug effects, physiology)