Urotensin II (U-II) and its
receptor GPR-14 were originally identified in the teleost fish, and were
recently shown to be present in several mammalian species. In the present
study we evaluated the role of the U-II/GPR-14 system in the regulation of
renal function and systemic hemodynamics in normal Wistar rats and in rats with
aorto-caval fistula, an experimental model of congestive heart failure (CHF).
The effects of incremental doses of human U-II (1.0- 100.0 nmole/kg) on mean
arterial pressure, renal hemodynamics (by ultrasonic flowmetery) and
intra-renal blood flow (by laser-Doppler methodology), as well as on renal
clearance parameters, were studied. In addition, the effects of prior blockade
of the nitric oxide (NO) system and prostaglandin synthesis, on the renal
hemodynamic response to U-II, were evaluated in CHF rats. Finally, we studied
the effects of U-II on selected cardiac parameters (by thermodilution
technique) in control rats. Our findings demonstrate that U-II exerts a marked
hypotensive effect both in control and CHF rats that was related to a decrease
in cardiac output, at least in control animals. In CHF rats, U-II caused a
significant, NO dependent, decrease in renal vascular resistance associated
with an increase in renal blood flow that was related in part to an increase in
medullary blood flow. U-II had no effects on renal sodium excretion either in
control or in CHF rats, but led to a significant increase in glomerular
filtration rate only in the CHF group. These findings suggest that the
U-II/GPR-14 system participates in the control of systemic and renal
hemodynamics in the rat, and that this regulation is significantly altered in
experimental CHF.
