Candesartan improves ischemia-induced impairment of the blood-brain barrier in vitro.

Abstract

Candesartan has been reported to have a protective effect on cerebral ischemia in vivo and in human ischemic stroke. We studied the direct effects of candesartan on blood-brain barrier (BBB) function with our in vitro monolayer model generated using rat brain capillary endothelial cells (RBECs). The in vitro BBB model was subjected to normoxia or 6-h oxygen glucose deprivation (OGD)/24-h reoxygenation, with or without candesartan. 6-h OGD/24-h reoxygenation decreased transendothelial electrical resistance and increased the endothelial permeability for sodium fluorescein in RBEC monolayers. Candesartan (10 nM) improved RBEC barrier dysfunction induced by 6-h OGD/24-h reoxygenation. Immunostaining and immunoblotting analysis indicated that the effect of candesartan on barrier function under 6-h OGD/24-h reoxygenation was not related to the expression levels of tight junction proteins. However, candesartan affected RBEC morphological changes induced by 6-h OGD/24-h reoxygenation. We analyzed oxidative stress and cell viability using chemical reagents. Candesartan improved cell viability following 6-h OGD/24-h reoxygenation, whereas candesartan had no effect on oxidative stress. These results show that candesartan directly improves cell function and viability of brain capillary endothelial cells under OGD/reoxygenation, suggesting that the protective effects of candesartan on ischemic stroke are related to protection of the BBB.

• Authors: Gohei So, Shinsuke Nakagawa, Yoichi Morofuji, Takeshi Hiu, Kentaro Hayashi, Kunihiko Tanaka, Kazuhiko Suyama, Maria A Deli, Izumi Nagata, Takayuki Matsuo, Masami Niwa
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 35 Issue 4 Pg. 563-72 (May 2015) ISSN: 1573-6830 [Electronic] United States
• PMID: 25547389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Biphenyl Compounds
• Nitrates
• Nitrites
• Reactive Oxygen Species
• Tetrazoles
• Tight Junction Proteins
• candesartan

Topics

• Animals
• Benzimidazoles (pharmacology)
• Biphenyl Compounds
• Blood-Brain Barrier (drug effects, pathology)
• Brain Ischemia (pathology)
• Cell Survival (drug effects)
• Electric Impedance
• Endothelial Cells (drug effects, metabolism, pathology)
• Nitrates (metabolism)
• Nitrites (metabolism)
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• Tetrazoles (pharmacology)
• Tight Junction Proteins (metabolism)
• Tight Junctions (drug effects, metabolism)