Interaction between reactive oxygen species and nitric oxide in the microvascular response to systemic hypoxia.
Systemic hypoxia results in oxidative stress due to a change in the reactive oxygen species (ROS)-nitric oxide (NO) balance. These experiments explored two mechanisms for the altered ROS-NO balance: 1) decreased NO synthesis by NO synthase due to limited O(2) substrate availability and 2) increased superoxide generation. ROS levels and leukocyte adherence in mesenteric venules of rats during hypoxia were studied in the absence and presence of an NO donor [spermine NONOate (SNO)] and of the NO precursor L-arginine. We hypothesized that if the lower NO levels during hypoxia were due to O(2) substrate limitation, L-arginine would not prevent hypoxia-induced microvascular responses. Graded hypoxia (produced by breathing 15, 10, and 7.5% O(2)) increased both ROS (123 +/- 6, 148 +/- 11, and 167 +/- 3% of control) and leukocyte adherence. ROS levels during breathing of 10 and 7.5% O(2) were significantly attenuated by SNO (105 +/- 6 and 108 +/- 3%, respectively) and L-arginine (117 +/- 5 and 115 +/- 2%, respectively). Both interventions reduced leukocyte adherence by similar degrees. The fact that the effects of L-arginine were similar to those of SNO does not support the idea that NO generation is impaired in hypoxia and suggests that tissue NO levels are depleted by the increased ROS during hypoxia.
Steiner
Dawn R S
DR
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Gonzalez
Norberto C
NC
Wood
John G
JG
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides; D011355:Prodrugs / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013152:Splanchnic Circulation; D014699:Venules / Q000503:physiopathology
D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D011355:Prodrugs; D017382:Reactive Oxygen Species; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D001120:Arginine