The peptide hormone urotensin II (UII) and its receptor GPR-14 have recently been identified in mammalian species, including man. Subsequent pharmacological studies have described profound cardiovascular and renal effects, suggesting a potential role in related disease states.
In the current study, anaesthetised (Intraval, 100 mg kg-1) Sprague-Dawley rats (n = 8 per group) were infused with 0.9 % saline (containing [3H]inulin as a marker of glomerular filtration rate (GFR) and para-aminohippuric acid as a marker of effective renal plasma flow) for 4 h prior to a single I.V. bolus injection of rat UII (10-10-10-9 M) or vehicle (0.9 % saline). Previous studies in our laboratory have shown significant changes in cardiofunction at 10-9 M but not at 10-10 M. Saline infusion lasted for a further 2 h. Urine samples were taken every 15 min and blood samples were taken in the middle of each hour. Blood pressure was monitored throughout. Plasma and urine electrolyte concentrations were measured. Animals were humanely killed at the end of the experiment.
All measured variables were in a steady state and did not differ between groups prior to injection of UII. Compared with values in the 15 min collection period prior to injection, UII at both 10-10 and 10-9 M caused significant (P < 0.05) dose-dependent decreases in GFR and urine flow rate in the 15 min after injection (Table 1). UII at 10-9 M also produced a significant (P < 0.05) reduction in effective renal blood flow and an increase in filtration fraction. Significant decreases in urinary Na+, K+, Ca2+ and Mg2+ clearance and excretion were also observed. There was no significant change in mean arterial blood pressure.
These data show that UII is able to exert profound effects on renal haemodynamic function and support the suggestion that UII may play a role in regulating cardiovascular and renal function.
