Oral administration of sepiapterin prevented concentric left ventricular hypertrophy and dilatory remodeling after transverse aortic constriction in rats by increasing the bioavailability of NO.
Does sepiapterin prevent left ventricular hypertrophy and dilatory remodeling in rats with pressure overload?
Sepiapterin prevents concentric left ventricular hypertrophy and dilatory remodeling in a rat model of pressure overload by increasing nitric oxide bioavailability.
Uncoupling of nitric oxide (NO) synthase (NOS) has been implicated in left ventricular (LV) hypertrophy (LVH) and dilatory remodeling induced by pressure overload. We investigated whether administration of sepiapterin, a substrate of the salvage pathway of tetrahydrobiopterin synthesis, prevents LVH and dilatory LV remodeling by inhibiting NOS uncoupling and increasing bioavailable NO. Pressure overload was induced in rats by transverse aortic constriction (TAC). Concentric LVH developed during 8 wk after TAC, and dilatory LV remodeling and dysfunction developed between 8 and 16 wk after TAC associated with a decrease in capillary density. Oral administration of sepiapterin or the superoxide/peroxynitrite scavenger N-(2-mercaptopropionyl)-glycine for 8 wk after TAC inhibited oxidative stress, but only sepiapterin increased bioavailable NO and inhibited cardiomyocyte hypertrophy associated with a further increase in capillary density. When sepiapterin was administered between 8 and 16 wk after TAC, cardiomyocyte hypertrophy was regressed and capillary density was restored. This was associated with the inhibition of interstitial fibrosis and dilatory LV remodeling. N-nitro-l-arginine methyl ester abrogated all the beneficial effects of sepiapterin in rats with TAC. These results suggest that sepiapterin prevents concentric LVH and dilatory remodeling after TAC primarily by increasing the bioavailability of NO.
Yoshioka et al. (Sat,) conducted a other in Left ventricular hypertrophy and dilatory remodeling induced by pressure overload. Sepiapterin vs. N-(2-mercaptopropionyl)-glycine or untreated TAC was evaluated on Left ventricular hypertrophy, dilatory remodeling, and bioavailable NO. Oral administration of sepiapterin prevented concentric left ventricular hypertrophy and dilatory remodeling after transverse aortic constriction in rats by increasing the bioavailability of NO.