Effects of urotensin II in human arteries and veins of varying caliber

Background-Urotensin II (UII) is the ligand for the GPR14 receptor and the most potent vasoconstrictor in the cynomolgus monkey. UII also contracts rat thoracic aorta. We studied the effect of human UII (hUII) in human blood vessels. Methods and Results-Small subcutaneous resistance arteries, internal mammary arteries, saphenous veins, and small subcutaneous veins were studied using standard techniques. Subcutaneous resistance arteries constricted in response to norepinephrine (maximum tension, 2.84 +/-0.38 mN/mm; the concentration 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 arteries, or either type of vein, but it was a patent vasoconstrictor in rat thoracic 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 actions of UII question its importance in human cardiovascular regulation.