Neuroprotective effect of nipradilol, an NO donor, on hypoxic-ischemic brain injury of neonatal rats.
Hypoxia-ischemia is a common cause of neonatal brain injuries. Nitric oxide (NO) is upregulated in the brain after hypoxia-ischemia and generally believed to exert a paradoxical effect on neurons, neurodestruction and neuroprotection, but it has not been demonstrated that NO is actually neuroprotective in neonatal hypoxic-ischemic encephalopathy. We evaluated the effect of intracerebroventricular administration of nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzopyran), a potent NO donor, at various concentrations (0.1 muM to 1 mM in 5 mul PBS/brain) to neonatal rats with hypoxic-ischemic treatment. The extent of the infarct area in the brain was significantly reduced by injection of the 1 muM nipradilol solution. However, denitro-nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)-propoxy-3-hydroxy-2H-1-benzopyran), that does not release NO, did not show the neuroprotective effect, suggesting that NO released from nipradilol exerts a neuroprotective effect on neonatal neurons.
Kakizawa
Hiroko
H
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Matsui
Fumiko
F
Tokita
Yoshihito
Y
Hirano
Kanako
K
Ida
Michiru
M
Nakanishi
Keiko
K
Watanabe
Masami
M
Sato
Yoshiaki
Y
Okumura
Akihisa
A
Kojima
Seiji
S
Oohira
Atsuhiko
A
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D011412:Propanolamines; D009569:Nitric Oxide; C036089:nipradilol