Endogenous renal urotensin II and its role in sodium and water handling in the young rat

Abstract

Urotensin II (UII) is a vasoactive peptide which has been implicated in human cardiovascular and renal disease. We have demonstrated a role for the urotensin II system in renal sodium and water regulation in the adult rat (Song et al. Kidney Int. 2006; 69: 1360–8). As urinary concentrating ability develops over the first few post-natal weeks in the rat, the aim of this study was to determine the role of endogenous UII in young rats. Young 4–5-week-old Sprague-Dawley rats were prepared for standard renal clearance experiments. Following a control period animals received either vehicle (NaCl 0.154M, n=6) or UII receptor (UT) antagonist SB706375 at 0.01mg.min−1. 100g bwt−1(n= 10) for 1h15min. UT antagonist caused a rapid, significant 50% increase in glomerular filtration rate (GFR) compared to vehicle-infused animals. Urine flow rate increased under antagonist infusion reaching a peak of 75.3±12.5 compared to 24.9±5.6 μl. min−1. 100g bwt−1during the control period (P<0.05). This diuresis was reflected by a smaller but significant 1.4-fold increase in sodium excretion rate during antagonist infusion. These data show that UT antagonism mediates both a diuresis and natriuresis in the young rat, the magnitude of which cannot be fully explained by the increased GFR. An indirect hemodynamic and a direct tubular role of the endogenous UII system is implicated in the immature kidney. Supported by an IMB capacity building award.