Superoxide dismutase mimetic tempol inhibits hypoxic pulmonary vasoconstriction in rats independently of nitric oxide production.
Hypoxic pulmonary vasoconstriction (HPV), an important physiological mechanism, is regulated by changes in the production of and interactions among reactive oxygen species (ROS). There is controversy, however, over whether HPV is mediated by an increase or a decrease in ROS production. Also, the role of NO in HPV remains unclear. The aim of this study was to investigate whether the inhibition of HPV by the antioxidant tempol was dependent on the concentration of NO, and how its effect was influenced by increased basal pulmonary vascular tone. In isolated rat lungs, we measured vasoconstrictor responses to acute ventilatory hypoxia before and after administration of tempol during perfusion with or without L-NAME. We found that tempol abolished HPV independently of NO production. When we increased basal vascular tone by K(+)-induced depolarization, we also found that tempol completely inhibited HPV. Our results indicate that inhibition of HPV by the superoxide dismutase mimetic tempol does not depend on either NO production or a decrease in basal vascular tone.
Hodyc
Daniel
D
Department of Physiology, Charles University, Second Medical School, Prague, Czech Republic. daniel.hodyc@lfmotol.cuni.cz
Snorek
Michal
M
Brtnický
Tomás
T
Herget
Jan
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D000975:Antioxidants; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013113:Spin Labels; D009569:Nitric Oxide; D013482:Superoxide Dismutase; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester