Modulation of hypoxic pulmonary vasoconstriction by antioxidant enzymes in red blood cells

Kazuhiro Yamaguchi, Koichiro Asano, Tomoaki Takasugi, Masaaki Mori, Hirofumi Fujita, Yoshitaka Oyamada, Koichi Suzuki, Atsushi Miyata, Takuya Aoki, Yukio Suzuki

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Abstract

To determine whether antioxidant mechanisms within red blood cells (RBCs) significantly contribute to preserving hypoxic pulmonary vasoconstriction (HPV) in both the absence and the presence of oxidative stress, we investigated HPV changes in isolated rabbit lungs perfused with solutions containing RBCs treated with various inhibitors of superoxide dismutase (SOD), anion channels, catalase (CAT), or glutathione peroxidase (GSH-Px). Perfusion was maintained at a constant flow rate of 70 ml/min, and lung temperature at 37 to 38° C. Hematocrit was adjusted to 7%. In the absence of overt oxidative stress, HPV was significantly enhanced in the perfusate containing control RBCs (untreated RBCs) as compared with that in Krebs- Henseleit buffer. Inhibition of SOD, CAT, and GSH-Px within RBCs, as well as anion channels located on the RBC membrane, had little influence on HPV. Neither exogenous SOD nor CAT altered HPV. In the presence of high levels of reactive oxygen species (ROS), generated by addition of xanthine (100 μM) and xanthine oxidase (10 mU/ml) to the reservoir, HPV was considerably suppressed in the perfusate containing only buffer but was restored in the perfusate with control RBCs. Inhibition of CAT or GSH-Px in RBCs preserved the HPV, whereas inhibition of SOD or anion channels failed to preserve HPV obtained during exposure to high ROS levels. Addition of exogenous SOD, but not CAT, to the perfusate containing RBCs in which endogenous SOD had been inhibited restored HPV under high ROS conditions. In conclusion, (1) although RBCs augment HPV in the absence of ROS, this finding is not attributable to the antioxidants in RBCs. (2) RBCs restore HPV upon exposure to high ROS. This finding may well be explained by antioxidant mechanisms operating within RBCs, especially those of endogenous SOD.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume153
Issue number1
Publication statusPublished - 1996

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Yamaguchi, K., Asano, K., Takasugi, T., Mori, M., Fujita, H., Oyamada, Y., Suzuki, K., Miyata, A., Aoki, T., & Suzuki, Y. (1996). Modulation of hypoxic pulmonary vasoconstriction by antioxidant enzymes in red blood cells. American Journal of Respiratory and Critical Care Medicine, 153(1), 211-217.