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Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen.

Publication ,  Journal Article
Demchenko, IT; Ruehle, A; Allen, BW; Vann, RD; Piantadosi, CA
Published in: J Appl Physiol (1985)
April 2009

Oxygen is a potent cerebral vasoconstrictor, but excessive exposure to hyperbaric oxygen (HBO(2)) can reverse this vasoconstriction by stimulating brain nitric oxide (NO) production, which increases cerebral blood flow (CBF)-a predictor of O(2) convulsions. We tested the hypothesis that phosphodiesterase (PDE)-5 blockers, specifically sildenafil and tadalafil, increase CBF in HBO(2) and accelerate seizure development. To estimate changes in cerebrovascular responses to hyperoxia, CBF was measured by hydrogen clearance in anesthetized rats, either control animals or those pretreated with one of these blockers, with the NO inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME), with the NO donor S-nitroso-N-acetylpenicillamine (SNAP), or with a blocker combined with l-NAME. Animals were exposed to 30% O(2) at 1 atm absolute (ATA) ("air") or to 100% O(2) at 4 or 6 ATA. EEG spikes indicated central nervous system CNS O(2) toxicity. The effects of PDE-5 blockade varied as a positive function of ambient Po(2). In air, CBF did not increase significantly, except after pretreatment with SNAP. However, at 6 ATA O(2), mean values for CBF increased and values for seizure latency decreased, both significantly; pretreatment with l-NAME abolished these effects. Conscious rats treated with sildenafil before HBO(2) were also more susceptible to CNS O(2) toxicity, as demonstrated by significantly shortened convulsive latency. Decreases in regional CBF reflect net vasoconstriction in the brain regions studied, since mean arterial pressures remained constant or increased throughout. Thus PDE-5 blockers oppose the protective vasoconstriction that is the initial response to hyperbaric hyperoxia, decreasing the safety of HBO(2) by hastening onset of CNS O(2) toxicity.

Duke Scholars

Published In

J Appl Physiol (1985)

DOI

ISSN

8750-7587

Publication Date

April 2009

Volume

106

Issue

4

Start / End Page

1234 / 1242

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Signal Transduction
  • Seizures
  • Rats, Sprague-Dawley
  • Rats
  • Physiology
  • Phosphodiesterase Inhibitors
  • Phosphodiesterase 5 Inhibitors
  • Nitric Oxide Synthase Type I
  • Male
 

Citation

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Chicago
ICMJE
MLA
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Demchenko, I. T., Ruehle, A., Allen, B. W., Vann, R. D., & Piantadosi, C. A. (2009). Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen. J Appl Physiol (1985), 106(4), 1234–1242. https://doi.org/10.1152/japplphysiol.91407.2008
Demchenko, Ivan T., Alex Ruehle, Barry W. Allen, Richard D. Vann, and Claude A. Piantadosi. “Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen.J Appl Physiol (1985) 106, no. 4 (April 2009): 1234–42. https://doi.org/10.1152/japplphysiol.91407.2008.
Demchenko IT, Ruehle A, Allen BW, Vann RD, Piantadosi CA. Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen. J Appl Physiol (1985). 2009 Apr;106(4):1234–42.
Demchenko, Ivan T., et al. “Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen.J Appl Physiol (1985), vol. 106, no. 4, Apr. 2009, pp. 1234–42. Pubmed, doi:10.1152/japplphysiol.91407.2008.
Demchenko IT, Ruehle A, Allen BW, Vann RD, Piantadosi CA. Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen. J Appl Physiol (1985). 2009 Apr;106(4):1234–1242.

Published In

J Appl Physiol (1985)

DOI

ISSN

8750-7587

Publication Date

April 2009

Volume

106

Issue

4

Start / End Page

1234 / 1242

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Signal Transduction
  • Seizures
  • Rats, Sprague-Dawley
  • Rats
  • Physiology
  • Phosphodiesterase Inhibitors
  • Phosphodiesterase 5 Inhibitors
  • Nitric Oxide Synthase Type I
  • Male