Effect of 7-nitroindazole sodium on the cellular distribution of neuronal nitric oxide synthase in the cerebral cortex of hypoxic newborn piglets.
Cerebral hypoxia results in generation of nitric oxide (NO) free radicals by Ca(++)-dependent activation of neuronal nitric oxide synthase (nNOS). The present study tests the hypothesis that the hypoxia-induced increased expression of nNOS in cortical neurons is mediated by NO. To test this hypothesis the cellular distribution of nNOS was determined immunohistochemically in the cerebral cortex of hypoxic newborn piglets with and without prior exposure to the selective nNOS inhibitor 7-nitroindazole sodium (7-NINA). Studies were conducted in newborn piglets, divided into normoxic (n = 6), normoxic treated with 7-NINA (n = 6), hypoxic (n = 6) and hypoxic pretreated with 7-NINA (n = 6). Hypoxia was induced by lowering the FiO(2) to 0.05-0.07 for 1 h. Cerebral tissue hypoxia was documented by decrease of ATP and phosphocreatine levels in both the hypoxic and 7-NINA pretreated hypoxic groups (P < 0.01). An increase in the number of nNOS immunoreactive neurons was observed in the frontal and parietal cortex of the hypoxic as compared to the normoxic groups (P < 0.05) which was attenuated by pretreatment with 7-NINA (P < 0.05 versus hypoxic). 7-NINA affected neither the cerebral energy metabolism nor the cellular distribution of nNOS in the cerebral cortex of normoxic animals. We conclude that nNOS expression in cortical neurons of hypoxic newborn piglets is NO-mediated. We speculate that nNOS inhibition by 7-NINA will protect against hypoxia-induced NO-mediated neuronal death.
Katsetos
Christos D
CD
Department of Pediatrics, Drexel University College of Medicine and St. Christopher's Hospital for Children, Philadelphia, PA, USA. Christos.Katsetos@DrexelMed.edu
Parikh
Nehal A
NA
Fritz
Karen I
KI
Legido
Agustin
A
Delivoria-Papadopoulos
Maria
M
Mishra
Om P
OP
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D007191:Indazoles / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D013552:Swine
D007191:Indazoles; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole