Basal release of endothelin-1 and the influence of the ET(B) receptor on single vessel hydraulic permeability

Gregory P. Victorino, David H Wisner, Vicky L. Tucker

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background: Endothelin-1 (ET-1) has a direct permeability decreasing effect on the microvasculature. The present study was designed to test the hypothesis that this effect is mediated via the endothelin B (ET(B)) receptor located on the microvascular endothelium and to determine whether basal microvascular permeability is dependent on constitutive release of ET-1. To isolate the direct effect of ET-1, experiments were conducted under conditions in which hydraulic and oncotic pressures were controlled. Methods: Postcapillary venules in the rat mesentery were perfused in situ, and paired measurements of hydraulic permeability (L(p)) were obtained using the modified Landis micro-occlusion method. L(p) measured after a 15-minute perfusion with the ET(B) receptor blocker BQ-788 (1 μmol/L) was compared with measures of L(p) obtained after perfusion with a combined mixture of BQ-788 and ET-1 (80 pmol/L) (n = 6). In addition, the effect of basal endogenous ET-1 was tested by measuring the effects of BQ-788 perfusion on L(p) (n = 6). Results: Units for L(p) are mean ± SE x 10-8 cm · s-1 · cm H2O-1. ET(B) receptor blockade prevented any decrease in L(p) induced by ET-1 (BQ-788 alone = 7.9 ± 0.7; BQ-788 + ET-1 = 8.2 ± 0.8; p = 0.5). Under basal conditions and in the absence of exogenous ET-1, ET(B) receptor blockade led to a significant increase in L(p) from 6.8 ± 0.9 to 9.7 ± 1.2 (p = 0.001). Conclusion: Decreases in microvascular permeability in single postcapillary venules after the administration of ET-1 are mediated via the ET(B) receptor. Constitutive release of ET-1 from the microvascular endothelium also plays a role in maintaining basal levels of permeability. These findings suggest important roles for ET-1 in maintaining and modulating microvascular permeability.

Original languageEnglish (US)
Pages (from-to)314-319
Number of pages6
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume49
Issue number2
StatePublished - 2000

Keywords

  • Capillary permeability
  • Endothelin
  • Endothelin receptor blocker
  • Endothelin receptors
  • Hydraulic conductivity
  • Landis technique

ASJC Scopus subject areas

  • Surgery

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