Preservation of cerebral blood flow responses to hypoxia and arterial pressure alterations in hyperammonemic rats

Takahiko Hirata, Raymond C. Koehler, Saul W. Brusilow, Richard J. Traystman

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13 Scopus citations


Acute hyperammonemia causes cerebral edema, elevated intracranial pressure and loss of cerebral blood flow (CBF) responsivity to CO2. Inhibition of glutamine synthetase prevents these abnormalities. If the loss of CO2 responsivity is secondary to the mechanical effects of edema, one would anticipate loss of responsivity to other physiological stimuli, such as hypoxia and changes in mean arterial blood pressure (MABP). To test this possibility, pentobarbital-anesthetized rats were subjected to either hypoxic hypoxia (P(a)O2 ≃ 30 mm Hg), hemorrhagic hypotension (MABP ≃ 70 and 50 mm Hg), or phenylephrine-induced hypertension (MABP ≃ 125 and 145 mm Hg). CBF was measured with radiolabeled microspheres. Experimental groups received intravenous ammonium acetate (≃50 μmol min-1 kg-1) for 6 h to increase plasma ammonia to 500-600 μM. Control groups received sodium acetate plus HCl to prevent metabolic alkalosis. The increase in CBF during 10 min of hypoxia after 6 h of ammonium acetate infusion (84 ± 19 to 259 ± 52 ml min-1 100 g-1) was similar to that after sodium acetate infusion (105 ± 20 to 265 ± 76 ml min-1 100 g-1). Cortical glutamine concentration was elevated equivalently in hyperammonemic rats subjected to normoxia only or to 10 min of hypoxia. With severe hypotension, CBF was unchanged in both the ammonium (80 ± 20 to 76 ± 24 ml min-1 100 g-1) and the sodium (80 ± 14 to 73 ± 16 ml min-1 100 g-1) acetate groups. With moderate hypertension, CBF was unchanged. With the most severe hypertension, significant increases in CBF occurred in both groups, but there was no difference between groups. We conclude that hypoxic and autoregulatory responses are intact during acute hyperammonemia. The previously observed loss of CO2 responsivity is not the result of a generalized vasoparalysis to all physiological stimuli.

Original languageEnglish (US)
Pages (from-to)835-844
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number5
StatePublished - 1995


  • Ammonia
  • Autoregulation
  • Glutamine
  • Hypoxia
  • Rats

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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