Proceedings of The Physiological Society

University of Manchester (2010) Proc Physiol Soc 19, C123

Oral Communications

The renal influence of endogenous urotensin II in the anaesthetised pre-hypertensive spontaneously hypertensive rat

E. Forty1, N. Ashton1

1. Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.

  • Table 1. Renal variables during initial control period (Cont) and final 15 min of UT-antagonist infusion period (Exp) in vehicle and antagonist-treated groups of young WKY and SHR. Data are mean±SEM, *P<0.05, **P<0.01, two-way ANOVA comparing control and experimental periods, vehicle vs antagonist treatment.

Urotensin II (UII) is a vasoactive peptide which has been implicated in cardiovascular and renal disease. Although its physiological role is still relatively unclear elevated plasma and urine concentrations of UII are correlated strongly with the incidence of essential hypertension. Infusion of rat UII causes an exaggerated renal response in the adult spontaneously hypertensive rat (SHR) compared to control Wistar-Kyoto (WKY) rats [1]. The aim of the current study was to establish the role of the renal UII system during the development of hypertension. Young 4-5-week-old WKY and pre-hypertensive SHR were anaesthetised with Inactin (10mg.100g bwt-1, i.p.) and prepared for standard renal clearance experiments. Animals were infused initially i.v. with 0.154M NaCl containing clearance markers at 40μl/min for a 2h45min equilibration period, before being randomly assigned to receive either vehicle (NaCl 0.154M, n=5 per strain) or UII receptor (UT) antagonist SB706375 at 0.01mg.min-1. 100g bwt-1(WKY n=6, SHR n=8) for 1h15min. Urine samples were collected every 15 min and two blood samples were taken per animal. Mean arterial pressure in young SHR was significantly higher (97±5 vs 82±5 mmHg, P<0.05) and the filtered load of ions was lower than in WKY before antagonist infusion. In the young SHR infusion of the UT antagonist significantly increased both urine flow and sodium excretion rates, independent of an effect on glomerular filtration rate or fractional sodium excretion (Table 1). In contrast there were no significant influences on any renal parameter during UT antagonist infusion compared to vehicle infusion in the young WKY (Table 1). Results suggest that UT antagonist influences renal sodium and water reabsorption independent of changes in filtered load in the SHR. The tonic influence of endogenous UII appears to be specific to the pre-hypertensive phenotype, as infusion of the UT antagonist does not influence renal function in the normotensive WKY rat. These data suggest that the UII system may contribute to renal sodium and water retention known to occur during the development of hypertension in the SHR.

Where applicable, experiments conform with Society ethical requirements