Cytoprotective effect of isotonic mannitol at low oxygen tension.
The beneficial effect of mannitol infusion in postischemic kidneys remains unresolved. Contradictory reports may have originated from at least 3 different mechanisms: a) arterial vasodilation, b) osmotic support of hypoxic cellular volume regulation, and c) scavenging of hydroxyl radicals in the reoxygenation period. To exclude vascular effects we tested at 37 degrees C in hypoxic (PO2 less than 1 mmHg) and reoxygenated isolated tubular cells of rat kidney cortex cellular function, i.e. intracellular K+ accumulation (K+), posthypoxic lactate gluconeogenesis (GNG), loss of membrane-bound tau-Glutamyltransferase (tau GT), and formation of a lipid peroxidation product, malondialdehyde (MDA). Mannitol (M) was added to a Ringer incubation medium in variable concentration either without (hypertonic M) or with omission of equiosmolar amounts of NaCl (isotonic M). K+ and GNG were significantly supported, and tau GT-loss markedly suppressed in a range of 10-50 mmol/l hypertonic and isotonic M. At higher concentrations no improvement (isotonic) or even deleterious effects (hypertonic) of M occurred. Beneficial effects of lower concentrations of M (10 mmol/l) were not correlated to anaerobic glycolysis, and 1 as well as 10 mmol/l M induced a comparable and significant reduction in posthypoxic MDA-formation. This effect was most pronounced when M was only added in hypoxia, indicating leakiness of cellular membranes in hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Gronow
G
G
Department of Physiology, University of Kiel, FRG.
Prechel
P
P
Klause
N
N
D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D003451:Cryoprotective Agents; D005609:Free Radicals; D005943:Gluconeogenesis / Q000187:drug effects; D006878:Hydroxides; D017665:Hydroxyl Radical; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D003451:Cryoprotective Agents; D005609:Free Radicals; D006878:Hydroxides; D006982:Hypertonic Solutions; D017665:Hydroxyl Radical; D008353:Mannitol; D008315:Malondialdehyde; D013012:Sorbitol; D005723:gamma-Glutamyltransferase; D011188:Potassium