Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide

David B. Pearse, Larissa A. Shimoda, Alexander D. Verin, Natalia Bogatcheva, Cheil Moon, Gabriele V. Ronnett, Laura E. Welsh, Patrice M. Becker

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The authors determined the effect of cyclic guanosine 3′,5′-monophosphate (cGMP) on hydrogen peroxide (H2O2)-induced barrier dysfunction in bovine lung microvascular endothelial cell (BLMVEC) monolayers and compared the results to bovine pulmonary artery endothelial cells (BPAECs). In BLMVECs, H2O2 (250 μM) caused a 31.9% ± 4.8% decrease in transendothelial electrical resistance (TER) associated with increased actin stress fiber formation, intercellular gaps, and intracellular calcium concentration ([Ca2+]i). The cGMP analogue 8-(p-chlorophenylthio)-cGMP (8p-CPT-cGMP; 30 or 50 μM) prevented the H2O2-induced decrease in TER (p < .001) as well as the cytoskeletal rearrangement and intercellular gap formation. 8-pCPT-cGMP (50 μM) attenuated the peak (418.8 ± 42.1 versus 665.2 ± 38.0 nmol/L; p < .001) and eliminated the sustained increase in [Ca2+]i (193.5 ± 21.3 versus 418.8 ± 42.1 nmol/L; p < .001) caused by H2O2. 8-pCPT-cGMP also increased TER (14.2% ± 2.2%; p < .05) and decreased [Ca2+]i (201.2 ± 12.5 vs. 214.4 ± 12.1 nmol/L; p < .03) before H2O2. In BPAECs, 8p-CPT-cGMP significantly attenuated H2O2-induced increases in permeability and [C2+]i but less effectively than in BLMVECs. These results suggest that in BLMVECs, cGMP countered the adverse effects of H2O2 on barrier function by preventing actin cytoskeletal rearrangement and attenuating the increase in [Ca2+]i.

Original languageEnglish (US)
Pages (from-to)309-317
Number of pages9
JournalEndothelium: Journal of Endothelial Cell Research
Volume10
Issue number6
DOIs
StatePublished - Jan 1 2003

Keywords

  • Calcium
  • Cytoskeleton
  • Pulmonary edema
  • cGMP-dependent protein kinases

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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