Brainstem nitric oxide tissue levels correlate with anoxia-induced gasping activity in the developing rat.
Gasping is an important mechanism for survival that appears to be developmentally modulated by the glutamate-nitric oxide (NO) pathway. However, the temporal characteristics of NO brain tissue levels during gasping are unknown. We hypothesized that during anoxia-induced gasping, the gasping frequency would be closely correlated with caudal brainstem tissue NO concentrations in developing rats. Brainstem and cortical tissue NO levels were measured during anoxia using a voltammetric electrode in adult rats and 5-day-old pups during control conditions and following pretreatment with the NMDA receptor antagonist MK-801 (1 mg/kg) or the neuronal NO synthase inhibitor 7-nitro-indazole (7-NI; 100 mg/kg). In young animals, NO tissue levels followed a triphasic trajectory coincident with gasp frequency which was markedly altered by MK-801 and 7-NI, albeit with preservation of gasp frequency-NO tissue level relationships. In adult rats, 40-fold higher NO tissue levels occurred and followed a monophasic trajectory coincident with gasp patterning. In the cortex, monophasic increases in NO levels occurred at all ages. We conclude that anoxia-induced gasping neurogenesis is modulated via NMDA-NO mechanisms in the developing rat. We postulate that higher NO brainstem concentrations may favor early autoresuscitation, but limit anoxic tolerance.
Gozal
D
D
Kosair Children's Hospital Research Institute, Departments of Pediatrics, Pharmacology and Toxicology, University of Louisville School of Medicine, KY 40202, USA. d0goza01@gwise.louisville.edu
Torres
J E
JE
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D019579:Neocortex / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012119:Respiration; D012120:Respiration Disorders / Q000209:etiology / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007191:Indazoles; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole