Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity.

ABSTRACT:

Rationale

Previously, we demonstrated that a deoxycorticosterone acetate (DOCA)-salt hypertensive mouse model produces cardiac oxidative stress and diastolic dysfunction with preserved systolic function. Oxidative stress has been shown to increase late inward sodium current (I(Na)), reducing the net cytosolic Ca(2+) efflux.

Objective

Oxidative stress in the DOCA-salt model may increase late I(Na), resulting in diastolic dysfunction amenable to treatment with ranolazine.

Methods and results

Echocardiography detected evidence of diastolic dysfunction in hypertensive mice that improved after treatment with ranolazine (E/E':sham, 31.9 ± 2.8, sham+ranolazine, 30.2 ± 1.9, DOCA-salt, 41.8 ± 2.6, and DOCA-salt+ranolazine, 31.9 ± 2.6; P=0.018). The end-diastolic pressure-volum

SUBMITTER: Lovelock JD 

PROVIDER: S-EPMC3314887 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature