Distribution of human i-NANC bronchodilator and nitric oxide-immunoreactive nerves.

We compared inhibitory nonadrenergic noncholinergic (i-NANC) neural relaxations, evoked by electrical field stimulation (EFS), at three levels (main [MA], proximal [PA], and distal [DA] airways) of isolated human airways and correlated these with nitric oxide synthase-immunoreactive (NOS-IR) nerves, using antiserum raised to rat cerebellar NOS. Maximal relaxations to papaverine (100 microM) were reduced in PA and DA (MA: 1,712 +/- 219 mg, n = 12; DA: 862 +/- 69 mg, n = 5, P < 0.05 versus MA); hence, subsequent relaxations were expressed as a percentage of the papaverine maximum. EFS elicited frequency-dependent relaxations that were largest in MA and reduced in PA and DA, especially at high stimulation frequencies (10 Hz EFS: MA: 51.6 +/- 3.7%, n = 12; PA: 30.5 +/- 6.0%, n = 6, P < 0.01 versus MA; DA: 17.8 +/- 3.6%, n = 5, P < 0.001 versus MA). The NOS inhibitor L-NG-nitroarginine methyl ester (L-NAME) (100 microM) and tetrodotoxin (3 microM) significantly inhibited i-NANC responses at all frequencies, le...