Dantrolene prevented left ventricular hypertrophy and improved impaired diastolic relaxation in pressure-overloaded mice by inhibiting RyR2-mediated diastolic calcium leakage.
Does dantrolene improve impaired diastolic function in mice with early pressure-overloaded hypertrophied hearts?
Dantrolene prevents hypertrophy progression and improves LV relaxation in a mouse model of pressure-overload hypertrophy by stabilizing RyR2.
Absolute Event Rate: 0% vs 0%
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.
Chang et al. (Thu,) reported a other. Dantrolene prevented left ventricular hypertrophy and improved impaired diastolic relaxation in pressure-overloaded mice by inhibiting RyR2-mediated diastolic calcium leakage.