Renal effects of human urotensin-II in rats with experimental congestive heart failure.
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.
Ovcharenko
Elena
E
Department of Physiology and Biophysics, Faculty of Medicine, Technion, IIT, PO Box 9649, Haifa, 31096, Israel.
Abassi
Zaid
Z
Rubinstein
Irith
I
Kaballa
Aviva
A
Hoffman
Aaron
A
Winaver
Joseph
J
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007677:Kidney Function Tests; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015854:Up-Regulation; D014563:Urodynamics; D014579:Urotensins / Q000378:metabolism / Q000494:pharmacology*
D014579:Urotensins; C029677:urotensin II; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin