No effect on central or peripheral blood pressure of systemic urotensin II infusion in humans

Jonathan T. Affolter, David E. Newby, Ian B. Wilkinson, Matthew J. Winter, Richard J. Balment, David J. Webb*

*Corresponding author for this work

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Aims: 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 ∼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.

Original languageEnglish
Pages (from-to)617-621
Number of pages5
JournalBritish Journal of Clinical Pharmacology
Volume54
Issue number6
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Arterial pressure
  • Cardiac output
  • Peptides
  • Vascular resistance
  • Vasoconstriction

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