Background-Urotensin II (UII) is the ligand for the GPR14 receptor and the
most potent vasoconstrictor in the cynomolgus monkey. UII also contracts ra
t thoracic aorta. We studied the effect of human UII (hUII) in human blood
vessels.
Methods and Results-Small subcutaneous resistance arteries, internal mammar
y arteries, saphenous veins, and small subcutaneous veins were studied usin
g standard techniques. Subcutaneous resistance arteries constricted in resp
onse to norepinephrine (maximum tension, 2.84 +/-0.38 mN/mm; the concentrat
ion required to produce 50% of the maximum response [EC50], 0.52 +/-0.07 mu
mol/L) and endothelin-1 (maximum tension, 4.19 +/- 10.93 mN/mm; EC50, 1.6
+/-0.1 nmol/L). hUII did not contract these arteries, internal mammary arte
ries, or either type of vein, but it was a patent vasoconstrictor in rat th
oracic aorta (maximum tension, 2.36 +/-0.2 mN/mm; EC50, 1.13 +/-0.36 nmol/L
).
Conclusions-hUII has no vasoconstrictor action in human arteries and veins
of different sizes and vascular beds. Marked species differences in the act
ions of UII question its importance in human cardiovascular regulation.