Urotensin II (UII) has been implicated in cardiovascular and renal disease [1] but its physiological role has yet to be fully explored. We have shown that UII has a marked effect on renal haemodynamics, resulting in a decrease in glomerular filtration rate (GFR) in Sprague Dawley rats [2]. At lower doses, which had only minimal effects on GFR, UII also increased fractional excretion of Na⁺ (FE_Na) [3]. Renal UII receptor (UT) mRNA expression is increased in SHR compared with Wistar-Kyoto (WKY) rats [2], suggesting that SHR may be more sensitive to UII. Hence, the aim of this study was to determine the renal response to UII in the SHR. Inactin anaesthetised (100 mg/kg, i.p.) male SHR and control normotensive WKY rats (n=7 per group) were infused with 0.154M NaCl containing ³H inulin (0.3 µCi/h) and para-aminohippuric acid (3mg/h) via a jugular vein catheter for 4 hours at 50 µl/min. Animals were then divided into three groups which received either vehicle, rUII at 0.6 or 6 pmol.min^-1.100g body weight^-1 for one hour. The infusate was then switched back to saline for a further hour. Urine samples were taken every 15 mins via a bladder catheter and blood samples were taken once per hour via a carotid artery catheter for the measurement of electrolytes. Animals were killed humanely at the end of the experiment. Mean arterial blood pressure was higher in SHR (214 ± 2) compared with WKY rats (117 ± 2 mmHg, P<0.001) and was unaffected by rUII. Basal effective renal blood flow (ERBF), GFR, urine flow (UV) and sodium excretion (U_NaV) rates were lower in SHR compared with WKY rats during vehicle infusion. Rat UII infused at 6 pmol.min^-1.100g bwt^-1 induced comparable reductions in the ERBF of SHR and WKY (Table 1). However, the reduction in GFR was significantly greater (P<0.05) in SHR; reductions in UV and U_NaV also tended to be greater. Interestingly, FE_Na increased in WKY rats but fell in SHR. The effects of rUII at 0.6 pmol.min^-1.100g bwt^-1 were similar but of smaller magnitude (data not shown). These data suggest that SHR are more sensitive to the renal haemodynamic effects of UII. The reduction in FE_Na observed in SHR in response to rUII contrasts with the increase in FE_Na seen in WKY, suggesting that UII may contribute to renal sodium retention in the SHR.