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)