Abstract 19210: Enhanced Denitrosylation Mitigates Cardiac Hypertrophy and Dysfunction During Chronic Pressure Overload

Protein S-nitrosylation (SNO) is a post-translational modification of protein thiol, which is a major effector mechanism of nitric oxide (NO) signaling. Level of protein SNO is controlled by S-nitrosoglutathione reductase (GSNOR). Recently, we showed that GSNOR mitigates intracellular calcium overload and LV remodeling and dysfunction induced by chronic β-adrenergic receptor (AR) stimulation. To further explore the role of protein SNO in LV remodeling and heart failure, we examined impact of chronic pressure overload induced by transverse aortic constriction (TAC) on cardiac function and hypertrophy in wild-type (WT, n=12), GSNOR-deficient (GSNOR, n=5) and GSNOR-transgenic (GSNOR-Tg, n=6) mice that overexpresses GSNOR restrictively in cardiomyocytes. Degree of LV hypertrophy and function was examined with serial echocardiography and postmortem examination 4 weeks after TAC. Before TAC, body weight, LV mass, and fractional shortening (FS) were similar in the three genotypes. TAC induced marked LV hypertrophy (LV mass; from 82±5 to 135±15mg, P