Effects of nicardipine treatment on Na(+)-K+ ATPase and lipid peroxidation after experimental subarachnoid haemorrhage.
The calcium theory of neuronal damage has been recently adapted to subarachnoid haemorrhage (SAH). It is proposed that haemorrhagic insult to the brain causes free radical-mediated destructive reactions of membrane phospholipids, and the consequent decrease of phospholipid-dependent enzymatic activities, such as Na(+)-K+ ATPase. In the present study we have studied the effects of Nicardipine treatment on lipid peroxidation and Na(+)-K+ ATPase activity after experimental induction of SAH. SAH was induced in anaesthesized rats by slow injection of 0.3 ml of autologous arterial blood into the cisterna magna. We assessed the extent of lipid peroxidation by measuring the level of thiobarbituric acid reactive substances (TBARS) and Na(+)-K+ ATPase activity in 3 different rat brain areas (cerebral cortex, hippocampus and brain stem) of sham-operated (0.3 ml of mock CSF into cisterna magna) and at 1 hour, 6 hours and 48 hours after SAH induction; simultaneously, we investigated the capacity of cerebral lipid peroxidation by measuring the accumulation of TBRAS in homogenates of brain areas incubated under aerobic conditions. Na(+)-K+ ATPase activity decreased in the cerebral cortex at 1 hour and 6 hours and in brain stem at 1 hour after SAH, while the same enzymatic activity did not change in the hippocampus. There was no significant difference in lipid peroxide content between sham-operated and haemorrhagic animals; Nicardipine treatment reduced the TBRAS content and induced the recovery of Na(+)-K+ ATPase activity, exerting a brain protective role against the detrimental effects of the haemorrhage.
Marzatico
F
F
Institute of Pharmacology, University of Pavia, I.R.C.C.S. Policlinico S. Matteo, Italy.
Gaetani
P
P
Spanu
G
G
Buratti
E
E
Rodriguez y Baena
R
R
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000201:enzymology*
D008054:Lipid Peroxides; D009529:Nicardipine; D000254:Sodium-Potassium-Exchanging ATPase