Hyperammonaemia reduces intracellular 22Na (sodium) ion and extracellular 86Rb ion concentrations in the blood-brain barrier of the rat.
Ammonia may be the major cerebral intoxicant responsible for the increased general or passive permeability of the blood-brain barrier (BBB) leading to the cerebral edema associated with acute liver failure. The present study investigated the effects of ammonia, as NH4+, on Na+ (22Na), K+ (86Rb), and 14C-mannitol uptake in the BBB. An in situ isolated perfused rat brain preparation was used to study the action of 1 mM ammonium acetate in Krebs'-Ringer perfusate. Passive water transport in the brain was studied by 14C-labeled mannitol uptake, a usually nondiffusible marker and active water transport by 22Na and 86Rb uptake. NH4+ significantly reduced 14C-mannitol uptake into the choroid plexus (P < 0.001) and increased it in the CSF (P < 0.05). Decreased 86Rb was measured in whole brain (P < 0.01) and CSF. However, no effect was observed in brain parenchyma, endothelium or choroid plexus thereby suggesting an increased efflux of 86Rb to the interstitial fluid. NH+ increased Na+ uptake into all areas of the brain studied. NH4+ does not increase the passive permeability into the BBB and was decreased in the choroid plexus. The increased 22Na+ uptake was substantiated by the observed decreases in 86Rb uptake in whole brain and CSF. This suggested NH4+ stimulates the Na+/K+ pump and increases extracellular Na+ concentrations and possibly intracellular concentrations with a concomitant decrease in K+ concentrations. These observations may provide a basis for the explanation of NH+ toxicity during hepatic encephalopathy and liver failure-induced cerebral edema.
Alexander
Barry
B
Department of Physiology, Sherrington School of Physiology, London, United Kingdom. barry.alexander@kcl.ac.uk
Smart
Kevin A
KA
Segal
Malcolm B
MB
Preston
Jane E
JE
D000641:Ammonia / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism; D004058:Diffusion / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D045604:Extracellular Fluid / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000378:metabolism*; D022124:Hyperammonemia / Q000139:chemically induced / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008353:Mannitol / Q000493:pharmacokinetics; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics*; D012979:Sodium Radioisotopes / Q000493:pharmacokinetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D002250:Carbon Radioisotopes; D012414:Rubidium Radioisotopes; D012979:Sodium Radioisotopes; D008353:Mannitol; D000641:Ammonia; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium