RHO-激酶抑制剂

Hydroxyfasudil hydrochloride is a ROCK inhibitor, with IC ₅₀ s of 0.73 and 0.72 μM for ROCK1 and ROCK2, respectively. Hydroxyfasudil also less potently inhibits PKA, with an IC ₅₀ of 37 μM, 50-fold higher than those of the ROCKs. Hydroxyfasudil increases eNOS mRNA levels, with an EC ₅₀ value of 0.8 ± 0.3 μM. Hydroxyfasudil (0-100 μM) concentration-dependently increases eNOS activity and stimulates NO production in human aortic endothelial cells (HAEC). Hydroxyfasudil (10 μM) increases the half-life of eNOS mRNA from 13 to 16 hours, but does not affect eNOS promoter activity at concentrations from 0.1 to 100 μM.

Hydroxyfasudil (10 mg/kg, i.p.) significantly increases both the average and maximal voided volumes in SD rats. Hydroxyfasudil also significantly decreases the maximal detrusor pressure. Hydroxyfasudil (3 mg/kg, i.p) inhibits hypercontractility induced by norepinephrine in spontaneously hypertensive rats (SHRs). Furthermore, Hydroxyfasudil (3, 10 mg/kg, i.p) significantly ameliorates decreased penile cGMP contents in rats.