Hydroxyfasudil Hydrochloride (HA 1100 hydrochloride) is a ROCK1/2 inhibitor (IC50s: 0.73/0.72 μM).

ROCK1:0.73 μM, ROCK2:0.72 μM

Hydroxyfasudil has a weak inhibition of PKA (IC50: 37 μM), 50-fold higher than those of the ROCKs. Hydroxyfasudil increases eNOS mRNA levels (EC50: 0.8 ± 0.3 μM). Hydroxyfasudil (0-100 μM) concentration-dependently increases eNOS activity and stimulates NO production in HAEC. Hydroxyfasudil (10 μM) increases the half-life of eNOS mRNA from 13 to 16 hours but does not affect eNOS promoter activity (0.1-100 μM).

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

Hydroxyfasudil is formulated in saline.Micturition behavior is studied after administration of either Hydroxyfasudil (10 mg/kg, i.p.) or a corresponding volume of saline. Each rat is placed in a metabolic cage containing a urine collection funnel that is placed over an electronic balance. The balance is connected to a personal computer via a multiport controller and used to measure the cumulative weight of the collected urine. Every 150 s during a continuous 24-h period, the computer samples and records the data for the micturition frequency and volumes. The micturition reflex parameters that are collected include: urine volume per micturition, maximal micturition volume, micturition frequency, and total urine output in the Hydroxyfasudil- or vehicle-treated animals. Each monitoring session started at 18.00 hours. Prior to being placed in the metabolic cage at the start of each experimental period, the animals received either a single injection of Hydroxyfasudil (10 mg/kg) dissolved in saline or an injection of saline without the inhibitor.