PHYSIOLOGICAL SIGNIFICANCE OF EPITHELIAL REMOVAL ON GUINEA-PIG TRACHEAL SMOOTH-MUSCLE RESPONSE TO ACETYLCHOLINE AND SEROTONIN

We studied the modulatory effect of airway epithelium on guinea pig tr acheal smooth muscle (TSM) contraction. Isometric force was measured i n vivo before and after removal of the tracheal epithelium. In paralle l studies, TSM contraction was also measured isometrically in epitheli um-intact and epithelium-denuded TSM strips in vitro. Epithelial remov al in vivo did not after the contractile response of TSM to acetylchol ine (ACh) or serotonin. In nine guinea pigs, active tension (AT) cause d by 3 x 10(-7) mol/kg of intravenous ACh was 0.74 +/- 0.14 g force pe r longitudinal length of the segment (g/cm) in the presence of epithel ium versus 0.89 +/- 0.16 g/cm after removal of airway epithelium (conf irmed histologically) (p NS). The threshold response to ACh was also u nchanged (-8.0 +/- 0.3 log mol/kg control versus -8.3 +/- 0.3 log mol/ kg after epithelial removal, p NS). In six guinea pigs, the AT caused by 3 x 10(-8) mol/kg of intravenous serotonin was 1.92 +/- 0.63 g/cm w ith an intact epithelium versus 2.15 +/- 0.70 g/cm after epithelial re moval in vivo (p NS). Epithelial removal in vitro increased the sensit ivity of TSM contraction to ACh when the data were expressed as the pe rcentage maximal response to ACh. The concentration of ACh causing 50% of the maximal response (EC50) was -5.74 +/- 0.25 log M in eight epit helium-intact TSM strips versus -6.37 +/- 0.16 log M after epithelial removal in controls (n = 8) (p = 0.05). However, removal of the trache al epithelium did not change the response to serotonin compared with e pithelium-intact TSM strips (n = 6) when the data were expressed as ab solute force or normalized as percentage maximal response. Epithelial removal also had no effect on force generation caused by either agonis t in vitro when normalized as percentage maximal response to electrica l field stimulation. We demonstrate that removal of airway epithelium in guinea pig trachea does not result in physiologically significant a ugmentation of the force of isometric TSM contraction either in vivo o r in vitro in response to two contractile agonists. Our data suggest t hat an epithelially derived relaxing factor does not cause physiologic ally significant inhibition of airway smooth muscle tone in the living state.