Effect of Exogenous Urotensin-II on Vascular Tone in Skin Microcirculation of Patients With Essential Hypertension

Background Plasma levels of urotensin-II (U-II) have been found to be elevated in patients with essential hypertension. However, the consequence of activation of the U-II system have not been previously determined in these patients. We therefore compared the effect of exogenous U-II administration on vascular tone in hypertensive patients (n = 13) and normotensive subjects (n = 14). Methods The effect of U-II on vascular tone was determined in the forearm skin microcirculation using iontophoresis to administer the drug and laser Doppler velocimetry to measure microvascular response. Results The U-II administration was associated with a dose-dependent vasodilator response from baseline in normotensive subjects (U-II 1 × 10−12 mol/L, 609 ± 164; U-II 1 × 10−9 mol/L, 839 ± 216; U-II, 1 × 10−7 mol/L, 1249 ± 228 arbitrary flux units; P< .0005). A dose-dependent vasoconstrictor response was observed in hypertensive patients compared to baseline (U-II 1 × 10−12 mol/L, 60 ± 212; U-II 1 × 10−9 mol/L, −288 ± 172; U-II, 1 × 10−7 mol/L, −607 ± 165 arbitrary flux units; P< .005). Differences in flow between the two groups were significant at the 1 × 10−9 mol/L and 1 × 10−7 mol/L dose levels (P< .001). In contrast, there was no significant difference in flux between baseline and U-II in either group (or between groups) when the opposite polarity was applied. Conclusions The demonstration of opposing effects of exogenous U-II in patients with hypertension and normal subjects suggests that U-II may be contributory to the increased vascular tone of these patients.