OBJECTIVE: Urotensin II (UII) is now recognized as the most potent human vasoconstrictor. Although its role in human pathophysiology is unknown, vasoactive mediators are known to be important in the pathogenesis of portal hypertension complicating chronic liver disease. The objective of this study was to investigate the role of UII in liver cirrhosis via examination of the in vivo effect of UII in this patient group. MATERIAL AND METHODS: The vasoactive effects of UII were measured using Laser Doppler velocimetry on cirrhotic patients (n = 14) and age-matched healthy controls (n = 14) after UII administration by iontophoresis to the cutaneous microcirculation of the forearm. RESULTS: In vivo administration of UII produced vasoconstriction of the cutaneous microcirculation in the cirrhotic group and vasodilatation in the controls, with values differing significantly at the two highest doses of UII: 10(-9) mol (p = 0.01) and 10(-7) mol (p = 0.004). CONCLUSIONS: UII mediates vasoconstriction of the microcirculation of cirrhotics but not of controls. This suggests that UII has pathophysiological relevance in the portal hypertensive population through its vasoactive properties. Further studies of UII and UII-antagonists are warranted in this patient population.
OBJECTIVE:Urotensin II (UII) is now recognized as the most potent human vasoconstrictor. Although its role in human pathophysiology is unknown, vasoactive mediators are known to be important in the pathogenesis of portal hypertension complicating chronic liver disease. The objective of this study was to investigate the role of UII in liver cirrhosis via examination of the in vivo effect of UII in this patient group. MATERIAL AND METHODS: The vasoactive effects of UII were measured using Laser Doppler velocimetry on cirrhotic patients (n = 14) and age-matched healthy controls (n = 14) after UII administration by iontophoresis to the cutaneous microcirculation of the forearm. RESULTS: In vivo administration of UII produced vasoconstriction of the cutaneous microcirculation in the cirrhotic group and vasodilatation in the controls, with values differing significantly at the two highest doses of UII: 10(-9) mol (p = 0.01) and 10(-7) mol (p = 0.004). CONCLUSIONS:UII mediates vasoconstriction of the microcirculation of cirrhotics but not of controls. This suggests that UII has pathophysiological relevance in the portal hypertensive population through its vasoactive properties. Further studies of UII and UII-antagonists are warranted in this patient population.
Authors: Joseph Cheriyan; Timothy J Burton; Timothy J Bradley; Sharon M L Wallace; Kaisa M Mäki-Petäjä; Isla S Mackenzie; Carmel M McEniery; John Brown; Ian B Wilkinson Journal: Br J Clin Pharmacol Date: 2009-10 Impact factor: 4.335