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Related Experiment Videos

Endothelin-mediated vasoconstriction in postischemic newborn intestine.

C A Nankervis1, G M Schauer, C E Miller

  • 1Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Ohio 43205, USA. nankervisc@pediatrics.ohio-state.edu

American Journal of Physiology. Gastrointestinal and Liver Physiology
|September 27, 2000
PubMed
Summary

Ischemia-reperfusion (I/R) in newborn swine intestine causes vasoconstriction due to endothelin-1 (ET-1) and loss of nitric oxide (NO) mediated by ET(B) receptors. Blocking ET(A) receptors with BQ-610 reduces this vasoconstriction in young swine.

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Area of Science:

  • Physiology
  • Vascular Biology
  • Neonatal Medicine

Background:

  • Ischemia-reperfusion (I/R) injury in neonatal intestine causes sustained vasoconstriction.
  • This vasoconstriction may result from loss of endothelium-derived nitric oxide (NO).
  • Endothelin-1 (ET-1) is a potential mediator of this constrictor tone.

Purpose of the Study:

  • To investigate if ET-1 is the unmasked constrictor after I/R in newborn swine intestine.
  • To determine if selective loss of endothelial ET(B) receptors contributes to I/R-induced hemodynamic changes.
  • To examine the role of ET-1 and ET(B) receptors in neonatal intestinal I/R.

Main Methods:

  • Studies in innervated, autoperfused intestinal loops in 3- and 35-day-old swine.
  • Pharmacological blockade of endothelin receptors using selective ET(A) antagonist BQ-610 and ET(B) antagonist BQ-788.

Related Experiment Videos

  • Assessment of hemodynamic parameters and oxygen consumption.
  • In vitro studies using mesenteric artery rings in myographs.

    • Main Results:

    • Selective blockade of ET(A) receptors with BQ-610 attenuated post-I/R vasoconstriction and reduced arteriovenous O(2) difference in 3-day-old swine.
    • Reduced tissue oxygen uptake did not affect the response to BQ-610 or ET-1 in young swine.
    • In vitro, blockade of ET(B) receptors with BQ-788 shifted the ET-1 dose-response curve leftward in 3-day-old swine, mimicking I/R effects.

    Conclusions:

    • Endothelin-1 (ET-1) likely mediates the vasoconstriction following ischemia-reperfusion (I/R) in the newborn swine intestine.
    • Loss of endothelial ET(B) receptors, which mediate nitric oxide (NO) vasodilation, contributes to the hemodynamic consequences of I/R.
    • Targeting ET(A) receptors may be a therapeutic strategy for I/R injury in neonates.