Effects of striatal nitric oxide production on regional cerebral blood flow and seizure development in rats exposed to extreme hyperoxia.
The endogenous vasodilator and signaling molecule nitric oxide has been implicated in cerebral hyperemia, sympathoexcitation, and seizures induced by hyperbaric oxygen (HBO2) at or above 3 atmospheres absolute (ATA). It is unknown whether these events in the onset of central nervous system oxygen toxicity originate within specific brain structures and whether blood flow is diverted to the brain from peripheral organs with high basal flow, such as the kidney. To explore these questions, total and regional cerebral blood flow (CBF) were measured in brain structures of the central autonomic network in anesthetized rats in HBO2 at 6 ATA. Electroencephalogram (EEG) recordings, cardiovascular hemodynamics, and renal blood flow (RBF) were also monitored. As expected, mean arterial blood pressure and total and regional CBF increased preceding EEG spikes while RBF was unaltered. Of the brain structures examined, the earliest rise in CBF occurred in the striatum, suggesting increased neuronal activation. Continuous unilateral or bilateral striatal infusion of the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester attenuated CBF responses in that structure, but global EEG discharges persisted and did not differ from controls. Our novel findings indicate that: 1) cerebral hyperemia in extreme HBO2 in rats does not occur at the expense of renal perfusion, highlighting the remarkable autoregulatory capability of the kidney, and 2) in spite of a sentinel increase in striatal blood flow, additional brain structure(s) likely govern the pathogenesis of HBO2-induced seizures because EEG discharge latency was unchanged by local blockade of striatal nitric oxide production and concomitant hyperemia.
Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Durham, North Carolina; Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; and heath.gasier@usuhs.edu.
Heath G
HG
Gasier
Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Durham, North Carolina; Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; and.
Ivan T
IT
Demchenko
Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Durham, North Carolina; Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; and.
Barry W
BW
Allen
Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Durham, North Carolina; Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; and Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Claude A
CA
Piantadosi
D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004569:Electroencephalography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology; D006931:Hyperbaric Oxygenation; D018496:Hyperoxia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D017072:Neostriatum / Q000098:blood supply* / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D012640:Seizures / Q000209:etiology / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester
Nω-nitro-l-arginine methyl ester; central autonomic network; neuroexcitation; nitric oxide; renal blood flow