Analysis of cardiovascular complications by the production of reactive oxygen species from mitochondria in patients with glucocrticoid excess

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10670663
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: AKAIKE Masashi University of Tokushima, Hospital, Instractor, 医学部・附属病院, 助手 (90271080)
• Co-Investigator(Kenkyū-buntansha): SHINTANI Yasumi University of Tokushima, School of Medicine, Assistant Professor, 医学部, 講師 (10235773)
• Project Period (FY): 1998 – 1999
• Keywords: Mitochondria / Respiratory chain / Reactive oxygen species / Glucocorticoid / Vascular endothelial cell / Vascular smooth muscle cell / Hypertension / Atherosclerosis

Research Abstract

The effect of glucbcrticoid excess on the production of reactive oxygen species (ROS), peroxynitrate and nitric oxide (NO) was investigated using the fluorescence probe (CM-HィイD22ィエD2DCFDA, DHR123 and DAF-2) in cultured human vascular endothelial cells from umbilical cord vein (HUVEO). The productions of ROS and peroxynitrate were significantly increased, but the production of NO was significantly decreased in 10ィイD1-7ィエD1M dexamethasone-treated HUVEC. Western blot analysis of 3-nitrotyrosine (foot print of peroxynitrate) showed increase of peroxynitrate in dexamethasone-treated HUVEC. Over-production by glucocorticoid excess was markedly suppressed by carbonyl cyanide m-chlorophenylhyazone, which could decrease ROS production from mitochondrial respiratory chain. Furthermore, the inhibition of complex I by diphenyleneiodinium chloride and the inhibition of complex 11 by thenoyltrifluoroadetone significantly decrease the over-production of ROS in dexamethasone-treated HLVEC. However, the inhibition of complex 111 by myxothiazol could not decrease the over-production of ROS in dexamethasone-treated HUVEC.
These findings showed that glucoeorticoid excess could cause the over-production of ROS from complex I and II in mitochondrial respiratory chain, and subsequently the consumption of NO in vascular endothekial cells. The production of ROS and consumption of NO by glucocorticoid excess could impair the vascular endothelial function, which may be a major pathogenesis for cardiovascular complications in patients with glucocorticoid excess.