Basal release of nitric oxide and its interaction with endothelin-1 on single vessel hydraulic permeability

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

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Both endothelin-1 (ET-1) and nitric oxide (NO) are released by the endothelium and are implicated in modulating the permeability of the endothelial barrier. The present study was designed to examine the interaction between ET-1 and NO and its influence on microvascular permeability as well as the role of NO in maintaining microvascular permeability. To isolate the direct effect of ET-1 and NO, experiments were conducted under conditions where hydraulic and oncotic pressures were controlled. Methods: Postcapillary venules in the rat mesentery were perfused in situ and paired measurements of hydraulic permeability (Lp) obtained using the modified Landis micro-occlusion method. The effect of basal endogenous NO was tested by measuring the effects of perfusion with the NO synthase inhibitor Nw-nitro-L-argininemethyl-ester (L-NAME) (100 μmol/L) on Lp (n = 6). In addition, Lp measured after a 15-minute perfusion with L-NAME (100 μmol/L) was compared with measures of Lp obtained after perfusion with a combined mixture of L-NAME (100 μmol/L) and ET-1 (80 pmol/L) (n = 6). Results: Units for Lp are mean ± SE × 10-8cm · sec-1 · cm H2O-1. Under basal conditions, in the absence of exogenous ET-1, NO synthase inhibition led to a significant increase in Lp from 5.7 ± 0.5 to 9.8 ± 1.4 (p = 0.02). Compared with L-NAME alone, ET-1 + L-NAME significantly decreased Lp from 10.3 ± 0.8 to 5.7 ± 0.6 (p = 0.006). Conclusion: Constitutive release of NO from the microvascular endothelium plays a role in maintaining a basal level of microvascular permeability. Decreases in microvascular permeability seen with the administration of ET-1 are not mediated via the release of NO. These findings suggest important roles for ET-1 and NO in maintaining and modulating microvascular permeability.

Original languageEnglish (US)
Pages (from-to)535-539
Number of pages5
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume50
Issue number3
StatePublished - 2001

Keywords

  • Capillary permeability
  • Endothelin
  • Hydraulic conductivity
  • L-NAME
  • Landis technique
  • Nitric oxide

ASJC Scopus subject areas

  • Surgery

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