Propofol stimulates ciliary motility via the nitric oxide-cyclic GMP pathway in cultured rat tracheal epithelial cells

Gotaro Shirakami, Dechun Li, Xinhua Zhan, Roger A. Johns

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Airway ciliary motility is impaired by inhaled anesthetics. Recent reports show that nitric oxide (NO) induces upregulation in ciliary beat frequency (CBF), and others report that propofol, an intravenous anesthetic, stimulates NO release; this raises the possibility that propofol increases CBF by stimulating the NO-cyclic guanosine monophosphate (cGMP) signal pathway. In this study, the authors investigated the effects of propofol on CBF and its relation with the NO-cGMP pathway using the pharmacologic blockers N(G)-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor; 1H-[1,2,4]oxidazole[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor; and KT5823, a cGMP-dependent protein kinase inhibitor, in cultured rat tracheal epithelial cells. Methods: Rat tracheal tissues were explanted and cultured for 3-5 days. Images of ciliated cells were videotaped using a phase-contrast microscope. Baseline CBF and CBF 25 min after exposure to propofol or blocker were measured using video analysis. Results: Vehicle (0.1% dimethyl sulfoxide; n = 11) increased CBF by 0.2 ± 1.7% (mean ± SD) from baseline. Propofol stimulated CBF significantly (P < 0.01) and dose dependently (1 μM, 2.0 ± 1.9%, n = 6; 10 μM, 8.2 ± 6.7%, n = 9; 100 μM, 14.0 ± 4.7%, n = 10). Intralipid (0.05%), the clinical vehicle of propofol, did not affect CBF (-0.2 ± 2.2%; n = 5). The enhancement of CBF with use of 100 μM propofol was abolished (P < 0.01) by coadministration of 10 mμM L-NMMA (2.4 ± 3.6%; n = 5), 100 μM ODQ (-0.3 ± 2.2%; n = 6) or 30 μM KT5823 (-0.1 ± 4.1%; n = 8). L-NMMA, ODQ, or KT5823 alone did not change CBF. Conclusions: These results show that propofol stimulates CBF via the NO-cGMP pathway in rat tracheal epithelial cells, suggesting a possible advantage of propofol in decreasing respiratory risk.

Original languageEnglish (US)
Pages (from-to)482-488
Number of pages7
JournalAnesthesiology
Volume93
Issue number2
DOIs
StatePublished - Jan 1 2000

Keywords

  • Airway epithelium
  • Ciliary movement
  • Soluble guanylyl cyclase

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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