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

Abstract

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). 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. The U-II administration was associated with a dose-dependent vasodilator response from baseline in normotensive subjects (U-II 1 x 10(-12) mol/L, 609 +/- 164; U-II 1 x 10(-9) mol/L, 839 +/- 216; U-II, 1 x 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 x 10(-12) mol/L, 60 +/- 212; U-II 1 x 10(-9) mol/L, -288 +/- 172; U-II, 1 x 10(-7) mol/L, -607 +/- 165 arbitrary flux units; P < .005). Differences in flow between the two groups were significant at the 1 x 10(-9) mol/L and 1 x 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. 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.