Medical Science & Innovation

Renamed from "The Bulletin of the Yamaguchi Medical School"

Yamaguchi University School of Medicine

EISSN:2758‐5441

Continues:The Bulletin of the Yamaguchi Medical School(vol. 1 ~ 69)
PISSN:0513-1812
EISSN:2436-696X

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Medical Science & Innovation Volume 70 Issue 1-2
published_at 2023-06

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

Dantrolene, a RyR2 stabilizer, restores impaired diastolic function in the pressure-verloaded hypertrophied heart
Chang Yaowei
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A050070000102
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.
Creator Keywords
ryanodine receptor
cardiac hypertrophy
calmodulin
DAN
pressure overload