Abstract: Objective Our previous study suggests that urotensin II (UII) plays a role in vasodilation when fluid volume in the body increases. To elucidate the role of UII in blood pressure regulation, we conducted this study using animal models that resemble the hemodynamic profiles of volume resistant and volume sensitive patients. In addition, a UII receptor knockout mouse model was established. Methods Dahl salt resistant (SR) rats, Dah1 salt sensitivity (SS) rats, wild type (WT) mice, and UII receptor knock out (KO) mice were used in this study. After placing these four groups of animals on a high salt diet for 6 or 8 weeks, renal
tissue was used to perform immunochemistry staining, real time PCR, and western blot to measure UII level in kidney. Results After high salt diet for 6 weeks, systolic blood pressure was significantly higher in SS group than in SR group (160±13 mmHg vs. 114±6 mmHg, t=8.191, P＜0.001). Compared with SS rats, SR
rats had higher plasma UII (60.3±3.8 vs. 51.6±13.5 pg/ml, t=2.450, P=0.021), urinary UII (236.9±27.89 ng/g vs. 114.70 ± 6.28 ng/g, t=3.898, P=0.003), 24 hours urinary sodium excretion (4w: 3.243 ± 0.306 mmol vs. 1.753±0.127 mmol, t=3.942, P=0.010; 6w: 2.870±0.134 mmol vs. 1.713±0.077 mmol, t=3.942, P＜0.001),
and urinary creatinine clearance (6w: 6.532±0.269 ml/min vs. 2.632±0.172 ml/min, t=12.210, P＜0.001). After high salt diet for 6 weeks, more UII receptor was expressed in renal tubular epithelia of SR rats as compared with those of SS rats (0.059±0.008 vs. 0.036±0.001, t=4.540, P=0.010). After high salt diet for 8 weeks, systolic blood pressure was significantly higher in KO mice than in WT mice (113 ± 3 mmHg vs. 102 ± 4mmHg, t=4.750, P=0.003). Conclusions The present results first demonstrate that UII can play a role in the regulation of blood pressure in Dah1 SR rats, probably through the effects of UII on ateriole dilatation and promotion of sodium excretion from renal tubules.

Key words: Urotensin II, Dahl salt-sensitive rat, Dahl salt-resistant rat, volume resistance-hypertension, UII receptor knock-out