Nitric oxide modulates anoxia-induced gasping in the developing rat.
Gasping is an important mechanism for survival. Nitric oxide (NO) plays an excitatory role in brainstem regions mediating respiratory responses to hypoxia. We hypothesized that neural structures mediating anoxia-induced gasping would display NO dependency. Two- to 15-day-old rat pups underwent anoxic exposures with 100% N2 in a plethysmograph following administration of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) blocker, L-arginine (L-Arg), a NO precursor, or normal saline. In general, gasp latencies were significantly shorter after L-Arg, and were prolonged with L-NAME. Furthermore, NOS inhibition prolonged gasping duration and reduced gasping frequency at all postnatal ages, although this effect was particularly increased with advancing postnatal age. NADPH-diaphorase staining and Western blots of protein lysates from the lateral tegmental field, the putative neural center underlying gasp generation, revealed progressively increased neuronal NOS abundance with animal maturation. We conclude that anoxia-induced gasping neurogenesis is modulated by NO mechanisms in neonatal pups. We postulate that higher NO brainstem concentrations may favor early autoresuscitation but be detrimental to overall survival during prolonged asphyxia.
Gozal
D
D
Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA. dgozal@tmcpop.tmc.tulane.edu
Torres
J E
JE
Gozal
E
E
Nuckton
T J
TJ
Dixon
M K
MK
Gozal
Y M
YM
Hornby
P J
PJ
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006651:Histocytochemistry; D000860:Hypoxia / Q000503:physiopathology*; D015151:Immunoblotting; D009252:NADPH Dehydrogenase / Q000032:analysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors; D051381:Rats; D012119:Respiration
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester