No effect on central or peripheral blood pressure of systemic urotensin II infusion in humans.
OBJECTIVE
In rodent and primate studies, urotensin II is an extremely potent vasoconstrictor peptide with effects in the central aortic and arterial vasculature as well as on cardiac function. The aim of the present study was to assess systemic haemodynamic responses to intravenous urotensin II infusion in humans.


METHODS
In 10 healthy male volunteers, intravenous urotensin II (3, 30 and 300 pmol min-1) and saline placebo were given on separate occasions in a single-blind randomized manner. Systemic haemodynamics and arterial stiffness were assessed by sphygmomanometry, transthoracic bioimpedance, and pulse wave analysis. Plasma urotensin II immuno-reactivity was measured by radio-immunoassay.


RESULTS
Intravenous urotensin II infusions were well tolerated with no adverse clinical effects and no electrocardiographic changes. Circulating plasma urotensin II immuno-reactivity increased from baseline of 16 +/- 1 to 1460 +/- 82 pmol l-1 (mean +/- s.e. mean) during infusion of urotensin II at 300 pmol min-1 (P < 0.001). However, there were no significant placebo adjusted changes in heart rate (95% confidence intervals: -3.6, + 4.4 min-1), mean arterial pressure (-5.8, + 1.7 mmHg) or cardiac index (-0.1, + 0.4 l min-1 m-2). There were also no changes in augmentation index (-4.1, + 5.2%) or pulse wave velocity (-1.3, + 0.3 m s-1).


CONCLUSIONS
Intravenous urotensin II infusion did not affect systemic haemodynamics or arterial stiffness, despite achieving an approximately 100-fold increase in plasma immuno-reactivity. We conclude that urotensin II is unlikely to have a physiological role in the short term regulation of vascular tone or blood pressure in man. Further confirmatory studies with urotensin II receptor antagonists are required.
Affolter
Jonathan T
JT
Clinical Research Centre, Department of Medical Sciences, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
Newby
David E
DE
Wilkinson
Ian B
IB
Winter
Matthew J
MJ
Balment
Richard J
RJ
Webb
David J
DJ
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D014579:Urotensins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D014579:Urotensins; D014662:Vasoconstrictor Agents; C029677:urotensin II