Cerebellar nitric oxide is increased during isoflurane anesthesia compared to halothane anesthesia: a microdialysis study in rats.
BACKGROUND
This study examined the influences of isoflurane versus halothane anesthesia on basal and agonist-stimulated nitric oxide in the cerebellum of intact rats. Nitric oxide was measured using the hemoglobin-trapping method in an in vivo microdialysis technique. This method uses the stoichiometric reaction of nitric oxide with oxyhemoglobin to produce methemoglobin and nitrate; the change in methemoglobin concentration is measured spectrophotometrically to estimate nitric oxide concentration.


METHODS
Male Wistar rats were anesthetized with isoflurane (1.4%) or halothane (1.2%), mechanically ventilated and paralyzed (intravenous pancuronium, 1 mg/kg). Microdialysis probes were implanted into the cerebellum. Bovine oxyhemoglobin dissolved in artificial cerebrospinal fluid was pumped through the probe (2 microl/min) and assayed at 15-min intervals. The glutamatergic agonist, kainic acid (KA, 5 mg/kg, intraarterially), was used to stimulate nitric oxide production. NG-nitro L-arginine methyl ester (L-NAME, 40 mg/kg, intravenously) was used to inhibit nitric oxide synthase.


RESULTS
Unstimulated cerebellar nitric oxide concentrations were stable and greater during anesthesia with isoflurane (532+/-31 nM; mean +/- SEM) than with halothane (303+/-23 nM). L-NAME pretreatment reduced nitric oxide concentrations during isoflurane, but not halothane, anesthesia. Infusion of KA increased nitric oxide in both groups; however, the increase in nitric oxide was significantly greater during isoflurane anesthesia. Pretreatment with L-NAME inhibited the response to KA in both groups.


CONCLUSIONS
Nitric oxide production in the cerebellum, monitored by microdialysis, was greater during isoflurane anesthesia than during halothane anesthesia. Increased nitric oxide production during isoflurane anesthesia would be expected to impact central neuronal function and cerebral blood flow and vascular resistance.
Loeb
A L
AL
Department of Anesthesia, University of Pennsylvania, Philadelphia, USA. loeb@cytometrics.com
Raj
N R
NR
Longnecker
D E
DE
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D018685:Anesthetics, Inhalation; D009569:Nitric Oxide; D007530:Isoflurane; D007608:Kainic Acid; D006221:Halothane; D019331:NG-Nitroarginine Methyl Ester