Physiological role of epithelium. In epithelium-intact tracheal rings, exposure to increased levels of ACh resulted in greater force production in both WT and Cav1 KO OVA mice, with much greater contractility in the absence of caveolin-1 (A). This was reflected by a significantly smaller effective concentration (EC50) of ACh in Cav1 KO mice, especially with OVA (B). Removal of epithelium reduced the EC50, but only in the WT CTL airways, suggesting dysfunctional epithelium or a lack of its role with inflammation and Cav1 KO. Accordingly, in epithelium intact rings, inhibition of NO synthase with NG-nitro-l-arginine methyl ester (l-NAME) enhanced baseline and peak force production by 1 μM ACh, but largely in WT CTL airways, and not in either Cav1 KO group (C). However, inhibition of arginase with N-omega-nor-l-arginine (nor-NOHA) substantially reduced the force responses to ACh in the Cav1 KO groups, especially with OVA (D). Values are means ± SE (n = 4 animals). *Significant difference between WT and Cav1 KO (P < 0.05). #Significant difference between CTL and OVA (P < 0.05). &Significant difference between epithelium intact and epithelium denuded rings (P < 0.05). $Significant difference between before and after inhibitor (l-NAME or nor-NOHA) treatment (P < 0.05).