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

Background: Airway ciliary motility is impaired by inhaled anesthetics. Rec ent reports show that nitric oxide (NO) induces upregulation in ciliary bea t frequency (CBF), and others report that propofol, an intravenous anesthet ic, stimulates NO release; this raises the possibility that propofol increa ses 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 bloc kers 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 inhibi tor; 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. Ima ges of ciliated cells were videotaped using a phase-contrast microscope. Ba seline CBF and CBF 25 min after exposure to propofol or blocker were measur ed 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 mu M, 2.0 +/- 1.9%, n = 6; 10 mu M, 8.2 +/ - 6.7%, n = 9; 100 mu M, 14.0 +/- 4.7%, n = 10). Intralipid (0.05%), the cl inical vehicle of propofol, did not affect CBF (-0.2 +/- 2.2%; n = 5). The enhancement of CBF with use of 100 mu M propofol was abolished (P < 0.01) b y coadministration of 10 m mu M L-NMMA (2.4 +/- 3.6%; n = 5), 100 mu M ODQ (-0.3 +/- 2.2%; n = 6) or 30 mu M KT5823 (-0.1 +/- 4.1%; n = 8), LMMA, ODQ, or KT5823 alone did not change CBF, Conclusions: These results show that propofol stimulates CBF via the NO-cGM P pathway in rat tracheal epithelial cells, suggesting a possible advantage of propofol in decreasing respiratory risk.