The Rho-kinase inhibitor Y27632 promotes ureteral relaxation in an in vivo rat model for partial ureteral obstruction.

Abstract

Aim of this study was to evaluate the effect of intravenous Y27632 (a ROK inhibitor) on intra-ureteral pressures and on blood pressure in an in vivo rat model for unilateral partial ureteral obstruction (PUO). 15 Male Sprague Dawley rats were used. Under isofluran anesthesia, saline was continuously infused via polyethylene (PE)-10 catheters inserted in the ureters beneath the kidney pelvis. Left psoas muscle was sutured around the distal left ureter to create a partial obstruction. Carotid artery and femoral vein were cannulated with PE catheters for registration of mean arterial blood pressure (MAP) and for administration of drugs. Left and right ureter pressures and MAP were simultaneously recorded. Y27632 (0.03 and 0.1mg/kg each n = 6-7) was given intravenously. T-test was used for comparisons. Spontaneous peristaltic pressure waves were recorded at baseline for both ureters. After the obstruction, Y27632 reduced maximum pressure (MaxP) by 10.5 ± 1.9% (0.03mg/kg; p = 0.004) and 29.1 ± 4.8% (0.1mg/kg; p < 0.001), minimum pressure (MinP) by 5.2 ± 2.3% (0.03mg/kg; p = 0.02) and 12.2 ± 3.4% (0.1mg/kg; p = 0.009), the area under the curve (AUC) by 7.8 ± 2.4% (0.03mg/kg; p = 0.008) and 16.5 ± 3.7% (0.1mg/kg;p = 0.007), the waves amplitude by 23.4 ± 11.3% (0.03mg/kg; p = 0.098) and 38.7 ± 7.5% (0.1mg/kg; p < 0.001), with no effect on contraction frequency. During simultaneous recordings from the normal ureter at the investigated doses, Y27632 reduced MaxP, MinP, AUC and waves amplitude by 1-7%. The MAP was reduced by 12.5 ± 5.3% (0.03mg/kg; p = 0.07) and 15.8 ± 1.8% (0.1mg/kg; p < 0.001). Y27632 decreased intra-ureteral pressures of a partially obstructed ureter with limited effect on blood pressure in an animal model of unilateral PUO.