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Suetomi Takeshi

Affiliate Master Yamaguchi University

Dantrolene, a RyR2 stabilizer, restores impaired diastolic function in the pressure-verloaded hypertrophied heart

Medical Science & Innovation Volume 70 Issue 1-2 Page 7-17
published_at 2023-06
A050070000102
[fulltext] 3.34 MB
Title
Dantrolene, a RyR2 stabilizer, restores impaired diastolic function in the pressure-verloaded hypertrophied heart
Abstract
To investigate whether dantrolene (DAN), cardiac ryanodine receptor (RyR2) stabilizer, improves impaired diastolic function in an early pressure-overloaded hypertrophied heart, pressure-overload hypertrophy was induced by transverse aortic constriction (TAC) in mice. Wild-type (WT) mice were divided into four groups: sham-operated mice (Sham), sham-operated mice treated with DAN (DAN+Sham), TAC mice (TAC), and TAC mice treated with DAN (DAN+TAC). The mice were then followed up for 2 weeks. Left ventricular (LV) hypertrophy was induced in TAC, but not DAN+TAC mice, 2 weeks after TAC. There were no differences in LV fractional shortening among the four groups. Catheter tip micromanometer showed that the time constant of LV pressure decay, an index of diastolic function, was significantly prolonged in TAC but not in DAN+TAC mice. Diastolic function was significantly impaired in TAC, but not in DAN+TAC mice as determined by cell shortening and Ca^{2+} transients. An increase in diastolic Ca^{2+} leakage and a decrease in calmodulin (CaM) binding affinity to RyR2 were observed in TAC mice, while diastolic Ca^{2+} leakage improved in DAN+TAC mice. Thus, DAN prevented the progression of hypertrophy and improved the impairment of LV relaxation by inhibiting diastolic Ca^{2+} leakage through RyR2 and the dissociation of CaM from RyR2.
Creators Chang Yaowei
Creators Kobayashi Shigeki
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Yano Yasutake
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Uchida Tomoyuki
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Nawata Junya
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Fujii Shohei
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Nakamura Yoshihide
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Suetomi Takeshi
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Uchinoumi Hitoshi
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Oda Tetsuro
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Yamamoto Takeshi
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Creators Yano Masafumi
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Source Identifiers
Creator Keywords
ryanodine receptor cardiac hypertrophy calmodulin DAN pressure overload
Languages eng
Resource Type departmental bulletin paper
Publishers Yamaguchi University School of Medicine
Date Issued 2023-06
File Version Version of Record
Access Rights open access
Funding Refs
China Scholarship Council (CSC)
Award
Schools 大学院医学系研究科(医学)