Calcium influx-dependent differential actions of superoxide and hydrogen peroxide on microvessel permeability

Xueping Zhou, Ke Wen, Dong Yuan, Ling Ai, Pingnian He

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Our previous study demonstrated that reactive oxygen species (ROS) released from activated blood cells contribute significantly to the increased microvessel permeability during inflammation. This study aims to define the individual roles of hydrogen peroxide (H 2O 2) and superoxide in ROS-induced increases in permeability and endothelial intracellular Ca 2+ concentration ([Ca 2+] i) in individually perfused rat mesenteric venules. Microvessel permeability was determined by measuring hydraulic conductivity (L p). Endothelial [Ca 2+] i was measured in fura-2 AM-loaded microvessels. Perfusing microvessels with superoxide generated by hypoxanthine and xanthine oxidase (HX/XO) induced immediate and transient increases in L p. The mean peak value, which occurred within 5 min of HX/XO exposure, was 4.3 ± 0.6 times that of the control. In contrast, the perfusion of H 2O 2 (100 and 500 μM) caused no immediate increases in L p. A significant L p increase, 3.6 ± 0.6 times the control value, occurred 30 min after the perfusion of H 2O 2 at 500 μM. The perfusion of H 2O 2 at 100 or 500 μM for 1 h increased L p to 6.6 ± 0.9 and 11.3 ± 3.6 times the control value, respectively. The increased endothelial [Ca 2+] i in HX/XO or H 2O 2 perfused vessels was correlated with the time course of the increases in L p. Inhibiting Ca 2+ influx by LaCl 3 prevented the permeability increase induced by HX/XO or H 2O 2. These results demonstrated differential actions of superoxide and H 2O 2 on microvessel permeability and endothelial [Ca 2+] i. Superoxide-induced permeability increases were immediate and transient, whereas H 2O 2- induced permeability increases were progressive, demonstrating concentration and time dependence. Ca 2+ influx plays an essential role in both superoxide and H 2O 2-induced permeability increases.

Original languageEnglish (US)
Pages (from-to)H1096-H1107
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume296
Issue number4
DOIs
StatePublished - Apr 2009

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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