title: Epithelial dependence of the bronchodilatory effect of sevoflurane and desflurane in rat distal bronchi.
abstract: The bronchial epithelium releases substances that enhance bronchodilation in response to certain bronchodilators. We examined the hypothesis that the bronchodilatory effect of desflurane and sevoflurane depends on the epithelium in rat distal bronchial segments. Wistar rat subsegmental bronchial segments (diameter approximately 100 microm) were dissected. After preconstriction with 5-hydroxytryptamine, each segment was exposed to increasing concentrations of desflurane 0%-12% or sevoflurane 0%-4.8% under four conditions: after epithelial rubbing, after pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (L-NNA), after pretreatment with the cyclooxygenase inhibitor indomethacin, or with no preintervention (control). Changes in bronchial diameter were monitored using an in vitro video detection system. Both desflurane and sevoflurane produced concentration-dependent bronchodilation (P < 0.001 for either anesthetic; 54% +/- 8% [mean +/- SD] dilation for 12% desflurane and 48% +/- 14% dilation for 4.8% sevoflurane). For both anesthetics, bronchodilation was significantly attenuated by epithelial rubbing (15% +/- 4% dilation for 12% desflurane and 13% +/- 10% dilation for 4.8% sevoflurane; P < 0.001 each), by pretreatment with indomethacin (12% +/- 3% dilation for 12% desflurane and 9% +/- 5% dilation for 4.8% sevoflurane; P < 0.001 each), and by L-NNA (24% +/- 8% dilation for 12% desflurane, P < 0.001; and 17% +/- 10% dilation for 4.8% sevoflurane, P < 0.01). Desflurane- and sevoflurane-mediated bronchodilation depends at least partially on the epithelium, and may involve both a prostanoid and NO in rat distal bronchi.
  
  
  CONCLUSIONS
  Bronchodilation by the volatile anesthetics desflurane and sevoflurane is at least partially epithelium-dependent and may be attenuated in diseases affecting the epithelium, such as asthma.
authors.affiliation: Department of Anesthesia & Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Park
authors.forename: H B
authors.initials: HB
authors.lastname: Dai
authors.forename: E
authors.initials: E
authors.lastname: Lowenstein
authors.forename: F W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D016084:Bronchoconstriction / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D000077335:Desflurane; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D008738:Methyl Ethers; D019335:Nitroarginine; D012701:Serotonin; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D007213:Indomethacin