Nitric oxide synthase inhibitors alter ventilation in isoflurane anesthetized rats.
BACKGROUND
Nitric oxide (NO) is present in medullary structures and can modulate respiratory rhythm. The authors determined if spontaneous ventilation at rest and in response to increased carbon dioxide is altered by selective neuronal NO synthase (NOS; 7-nitro-indazole, 7-NI) or nonselective (neuronal plus endothelial) NOS (NG-L-arginine methyl ester [L-NAME] and NG-monomethyl L-arginine [L-NMMA]) inhibitors in rats anesthetized with isoflurane.


METHODS
Fifty-four rats received either L-NAME or L-NMMA (1, 10, and 30 mg/kg) or 7-NI (20, 80, and 400 mg/kg) and were compared with time controls (isoflurane = 1.4%), with isoflurane concentrations (1.6%, 1.8%, and 2%) increased consistent with the increased anesthetic depth caused by NOS inhibitors, or with L-arginine (300 mg/kg). Tidal volume (VT), respiratory frequency (f), minute ventilation (VE), and ventilatory responses to increasing carbon dioxide were determined.


RESULTS
L-NAME and L-NMMA decreased resting VT and VE, whereas 7-NI had no effect. Increasing concentrations of isoflurane decreased resting f, VT, and VE. L-NAME and L-NMMA decreased VT and VE, whereas 7-NI had no effect at 8%, 9%, and 10% end-tidal carbon dioxide (ETCO2). Increasing concentrations of isoflurane decreased f, VT, and VE at 8%, 9%, and 10% ETCO2. The slope of VE versus ETCO2 was decreased by isoflurane but was unaffected by L-NAME, L-NMMA, or 7-NI. L-arginine alone had no effect on ventilation.


CONCLUSIONS
Nonselective NOS inhibitors decreased VT and VE at rest and at increased carbon dioxide levels but did not alter the slope of the carbon dioxide response. Selective neuronal NOS inhibition had no effect, suggesting that endothelial NOS may be the isoform responsible for altering ventilation. Finally, the cause of the decreased ventilation is not a result of the enhanced anesthetic depth caused by NOS inhibitors.
Patel
G M
GM
Department of Anesthesiology, University of Virginia Health System, Charlottesville 22906-0010, USA.
Horstman
D J
DJ
Adams
J M
JM
Rich
G F
GF
D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007191:Indazoles / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D007191:Indazoles; D002245:Carbon Dioxide; D019323:omega-N-Methylarginine; D001120:Arginine; D007530:Isoflurane; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester