Stress-induced increase in extracellular sucrose space in rats is mediated by nitric oxide.
Exposure to physical or psychological stress causes brain damage ranging from minimal behavioural alterations to neurodegeneration. One of the proposed mechanisms for stress-induced neurodegeneration is the overproduction of nitric oxide (NO) and related oxidative-nitrosative compounds via expression of the inducible NO synthase (iNOS). In the present investigation, the effect of acute or chronic immobilisation on blood-brain barrier (BBB) permeability and the possible role of iNOS were studied in adult male Wistar rats. Stress-induced [(14)C]-sucrose uptake by brain tissue correlates with the production of the stable NO metabolites nitrite and nitrate in both peripheral (plasma) and central (brain) compartments. Injection of the specific iNOS inhibitor 1400W (2 mg/kg, i.p.) prevents the stress-induced increase in BBB permeability. Taken together, these findings indicate that iNOS expression mediates stress-induced increase in BBB permeability and support a possible neuroprotective role for specific iNOS inhibitors in this situation.
Madrigal
José L M
JL
Departmento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid 28040, Spain.
Moro
María A
MA
Lizasoain
Ignacio
I
Lorenzo
Pedro
P
Leza
Juan C
JC
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001812:Blood-Brain Barrier; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013312:Stress, Physiological; D013395:Sucrose / Q000378:metabolism*
D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009566:Nitrates; D009573:Nitrites; D013395:Sucrose; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat