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

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

Research output: Contribution to journalArticle

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
StatePublished - 2003

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Guanosine Monophosphate
Hydrogen Peroxide
Lung
Electric Impedance
Endothelial Cells
Pulmonary Artery
Actins
Stress Fibers
Permeability
Calcium

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide. / Pearse, David B; Shimoda, Larissa; Verin, Alexander D.; Bogatcheva, Natalia; Moon, Cheil; Ronnett, Gabriele V.; Welsh, Laura E.; Becker, Patrice M.

In: Endothelium: Journal of Endothelial Cell Research, Vol. 10, No. 6, 2003, p. 309-317.

Research output: Contribution to journalArticle

Pearse, DB, Shimoda, L, Verin, AD, Bogatcheva, N, Moon, C, Ronnett, GV, Welsh, LE & Becker, PM 2003, 'Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide', Endothelium: Journal of Endothelial Cell Research, vol. 10, no. 6, pp. 309-317.
Pearse, David B ; Shimoda, Larissa ; Verin, Alexander D. ; Bogatcheva, Natalia ; Moon, Cheil ; Ronnett, Gabriele V. ; Welsh, Laura E. ; Becker, Patrice M. / Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide. In: Endothelium: Journal of Endothelial Cell Research. 2003 ; Vol. 10, No. 6. pp. 309-317.
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AB - 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.

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