Renal actions of endogenous urotensin II in the anaesthetised pre-hypertensive spontaneously hypertensive rat.

Ellen Forty, Nick Ashton. The University of Manchester, Manchester, United Kingdom.

Urotensin II (UII) acts on both the renal vasculature and tubular epithelium to conserve salt and water. The adult spontaneously hypertensive rat (SHR) responds to infusion of rat UII with greater decreases in renal water and sodium excretion compared to control Wistar-Kyoto (WKY) rats (Abdel-Razik et al., 2008, Am J Physiol 295:F1239-47). These data suggest that UII may play a role in established hypertension; however, its role in the development of hypertension is unknown. Inactin-anaesthetised (10mg. 100g bwt-1 i.p) young 4-5-week-old male WKY and SHR were prepared for a standard renal clearance experiment. Following an initial 2h equilibration period and a 45min control period animals were randomly assigned to receive either vehicle (0.154M NaCl at 40μl/min, n= 5 per strain) or UII receptor antagonist SB706375 at 0.01mg.min-1. 100g bwt-1 (WKY n=6, SHR n=8) for 75min. Renal parameters in vehicle-infused rats of both strains remained steady throughout the experiment. Antagonist infusion caused an increase in glomerular filtration rate (GFR), effective renal blood flow (ERBF) and urine flow rate (UV) in WKY rats, but theses effects did not reach significance (Table 1). However, antagonist infusion in SHRs significantly increased GFR, UV and sodium excretion rate (UNaV); there was also a tendency towards an increase in ERBF and fractional sodium excretion (FENa) (Table 1). These data suggest that endogenous UII has a tonic influence on renal function in the young SHR. The marked diuresis and natriuresis observed in young SHR was associated with only a moderate increase in GFR which, coupled with a tendency towards an increase in FENa, suggests that endogenous UII affects tubular reabsorption of sodium. In contrast the effect of the UII receptor antagonist was less obvious in WKY rats, suggesting that endogenous UII has a lesser role in regulating kidney function in the young normotensive rat. These results indicate that UII may contribute to renal sodium retention in the young pre-hypertensive SHR.