NOS Inhibitors Decrease Hypoxia-induced ATP Reductions in Respiring Cerebrocortical Slices

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BackgroundExcess neuronal nitric oxide (NO) production might cause adenosine triphosphate loss and cellular damage in hypoxic brain parenchyma. (31) P nuclear magnetic resonance spectroscopy was used to study hypoxic intracellular responses in perfused respiring cerebrocortical slices, in which NO scavenging by hemoglobin is absent, during NO synthase blockade and NO augmentation.MethodsAdenosine triphosphate concentrations were monitored at 4.7 Tesla in respiring slices before, during, and after 60 min of hypoxia (oxygen tension < 5 mmHg). Slices were not treated or were pretreated with 27 [micro sign]M L-nitroarginine methyl ester (L-NAME), 27 [micro sign]M 7-nitroindozole (7-NI), or 27 [micro sign]M L-nitroarginine. Nitrotyrosine:tyrosine ratios of slice extracts were measured using high-performance liquid chromatography. Cresyl violet-stained sections (2 [micro sign]m) from random slices were examined histologically.ResultsAfter 60 min of hypoxia, adenosine triphosphate decreased to ConclusionNeuronal NO is associated with rapid adenosine triphosphate reductions and peroxynitrite formation in acutely hypoxic cerebrocortical slices.

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