BACKGROUND: Urotensin II (U-II) and its receptor GPR-14 are expressed in the kidney and the cardiovascular system of various mammalian species. Recent studies suggested that the U-II/GPR-14 system is upregulated in patients with congestive heart failure (CHF). However, the involvement of the peptide in the alterations of renal function in CHF remains unknown. METHODS: The effects of incremental doses (1.0-100.0 nmol/kg) of human U-II (hU-II) on renal haemodynamic and clearance parameters were assessed in rats with an aorto-caval fistula, an experimental model of CHF, and sham controls. Additionally, the effects of pre-treatment with the nitric oxide (NO) synthase blocker, nitro-L-arginine methyl ester (L-NAME), and the cyclooxygenase inhibitor, indomethacin, on the renal haemodynamic response to hU-II were studied in CHF rats. RESULTS: hU-II caused a decrease in mean arterial pressure in control and CHF rats. In controls, hU-II did not alter renal blood flow (RBF), and caused a minimal decrease (-12.5%) in renal vascular resistance (RVR). However, in CHF rats, the peptide induced a marked increase in RBF (+28%) and a decrease in RVR (-21.5%). These effects were attenuated by L-NAME, but not by indomethacin. Furthermore, hU-II caused a significant increase (+29%) in glomerular filtration rate (GFR) in CHF rats, whereas GFR tended to decrease in controls. Sodium excretion was not altered in control or in CHF rats in response to hU-II. CONCLUSIONS: hU-II exerts an NO-dependent renal vasodilatation that is more pronounced in rats with CHF. The data further suggest that the U-II/GPR-14 system may be involved in the regulation of renal haemodynamics in CHF.
BACKGROUND:Urotensin II (U-II) and its receptor GPR-14 are expressed in the kidney and the cardiovascular system of various mammalian species. Recent studies suggested that the U-II/GPR-14 system is upregulated in patients with congestive heart failure (CHF). However, the involvement of the peptide in the alterations of renal function in CHF remains unknown. METHODS: The effects of incremental doses (1.0-100.0 nmol/kg) of humanU-II (hU-II) on renal haemodynamic and clearance parameters were assessed in rats with an aorto-caval fistula, an experimental model of CHF, and sham controls. Additionally, the effects of pre-treatment with the nitric oxide (NO) synthase blocker, nitro-L-arginine methyl ester (L-NAME), and the cyclooxygenase inhibitor, indomethacin, on the renal haemodynamic response to hU-II were studied in CHFrats. RESULTS:hU-II caused a decrease in mean arterial pressure in control and CHFrats. In controls, hU-II did not alter renal blood flow (RBF), and caused a minimal decrease (-12.5%) in renal vascular resistance (RVR). However, in CHFrats, the peptide induced a marked increase in RBF (+28%) and a decrease in RVR (-21.5%). These effects were attenuated by L-NAME, but not by indomethacin. Furthermore, hU-II caused a significant increase (+29%) in glomerular filtration rate (GFR) in CHFrats, whereas GFR tended to decrease in controls. Sodium excretion was not altered in control or in CHFrats in response to hU-II. CONCLUSIONS:hU-II exerts an NO-dependent renal vasodilatation that is more pronounced in rats with CHF. The data further suggest that the U-II/GPR-14 system may be involved in the regulation of renal haemodynamics in CHF.