The potent vasoregulatory mediator urotensin-II is produced in the fetus and demonstrates a delayed increase after birth

  • Dr Catherine Simpson, Murdoch Childrens Research Institute, Melbourne, Australia, Australia
  • A/Prof Joseph Smolich, Murdoch Childrens Research Institute, Melbourne, Australia, Australia
  • Mr Andrew Hattam, Murdoch Childrens Research Institute, Melbourne, Australia, Australia
  • Dr Lara Shekerdemian, The Royal Children's Hopsital, Melbourne, Australia
  • Prof Daniel Penny, The Royal Children's Hopsital, Melbourne, Australia

    • OBJECTIVE:
    The mediators involved in perinatal regulation of vascular function are incompletely understood, although enothelin-1 (ET-1) is known to be important. Another potent vasoactive agent, urotensin-II (U-II), has been implicated in regulation of vascular tone, but its potential roles in the fetus or in circulatory adjustments at birth are unknown. The aims of this study were to determine if U-II was produced by the fetus and to compare changes in circulating U-II and ET-1 levels at birth.

    METHODS:
    Eighteen anaesthetised fetal lambs were instrumented with aortic and pulmonary arterial (PA) catheters for blood sampling and pressure measurement. In seven fetuses blood was simultaneously sampled from the ewe’s carotid artery. In a subgroup of eight lambs, PA blood samples were taken 0.5, 1 and 4 hr after delivery by caesarean-section. Plasma U-II and ET-1 concentrations were measured by radioimmunoassay.

    RESULTS:
    In fetuses, PA and aortic U-II levels were near-identical (1.29±0.4 vs. 1.28±0.35 pmol/L), and were higher than in ewes (0.72±0.3 pmol/L, p<0.02). After birth, in conjunction with a reduced PA (p<0.006) and unchanged aortic blood pressure (p>0.3), ET-1 levels at all postnatal time points were greater than in the fetus (p<0.001). By contrast, U-II levels were unchanged from the fetus at 0.5 and 1hr, but were greater by 4 hr (p=0.01).

    CONCLUSIONS:
    These findings suggest that the fetus produces U-II. However, the delayed elevation of circulating U-II levels following delivery implies that, unlike ET-1, this agent may not play a major role in the immediate haemodynamic changes at birth.