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H2O2 causes endothelial barrier dysfunction without disrupting the arginine-nitric oxide pathway
M P Gupta1, H O Steinberg, C M Hart
1Department of Medicine, Indiana University, Indianapolis, USA.
The American Journal of Physiology
|May 12, 1998
Summary
Hydrogen peroxide (H2O2) impairs endothelial cell barrier function but does not inhibit nitric oxide synthase (NOS) activity. The arginine-nitric oxide pathway remains functional in pulmonary artery endothelial cells (PAECs) under oxidant stress.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Physiology
- Oxidative Stress Research
Background:
- Nitric oxide (NO) donors protect against, while nitric oxide synthase (NOS) inhibition worsens, hydrogen peroxide (H2O2)-induced injury in porcine pulmonary artery endothelial cells (PAECs).
- Previous findings suggest a complex interplay between NO signaling and oxidant stress in endothelial cells.
Purpose of the Study:
- To investigate if oxidant-mediated inhibition of NOS contributes to H2O2-induced PAEC injury.
- To determine the effect of H2O2 on NOS activity and the arginine-NO pathway in PAECs.
Main Methods:
- PAEC barrier function was assessed by measuring transmonolayer albumin clearance.
- NOS activity was measured using [3H]arginine to [3H]citrulline conversion in PAEC lysates and intact cells.
- Guanylate cyclase activity and NO release were assessed in H2O2-treated PAECs.
Main Results:
- H2O2 (10-100 microM) significantly impaired PAEC barrier function without causing cytotoxicity.
- H2O2 treatment did not alter NOS activity in PAEC lysates or intact cells.
- H2O2 had minimal effects on guanylate cyclase activity and NO release, indicating the arginine-NO pathway remained intact.
Conclusions:
- Oxidant-mediated inhibition of NOS does not appear to be the primary mechanism underlying H2O2-induced PAEC injury.
- The arginine-NO pathway remains functional in PAECs exposed to oxidant conditions that disrupt endothelial cell function.