DISTRIBUTION OF HUMAN I-NANC BRONCHODILATOR AND NITRIC OXIDE-IMMUNOREACTIVE NERVES

We compared inhibitory nonadrenergic noncholinergic (i-NANC) neural re laxations, evoked by electrical field stimulation (EFS), at three leve ls (main [MA], proximal [Ph], and distal [DA] airways) of isolated hum an airways and correlated these with nitric oxide synthase-immunoreact ive (NOS-IR) nerves, using antiserum raised to rat cerebellar NOS, Max imal relaxations to papaverine (100 mu M) were reduced in PA and DA (M A: 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 t hat were largest in MA and reduced in PA and DA, especially at high st imulation 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 < 0.0 01 versus MA). The NOS inhibitor L-N-G-nitroarginine methyl ester (L-N AME) (100 mu M) and tetrodotoxin (3 mu M) significantly inhibited i-NA NC responses at all frequencies, leaving an L-NAME-resistant non-neura l relaxation at frequencies > 5 Hz which was reduced in PA and DA. Cum ulative concentration-response studies to sodium nitroprusside (1 nM t o 0.1 mM) and the NO donor 3-morpholinosydnonimine (1 nM to 1 mM) were not significantly different in PA and DA, suggesting impaired relaxat ion is not caused by impaired guanylyl cyclase activity. Total nerve d ensity, shown by protein gene product 9.5 staining, was not significan tly different in PA and DA; however, NOS-IR nerve density was reduced in PA and DA (NOS-IR [intercepts/mm(2)]: MA: 705 +/- 98, n = 6; DA: 28 4 +/- 32, n = 6, P < 0.01 versus MA). These studies demonstrate that i NANC neural relaxations are reduced in DA, apparently due to a decrea se in the density of nitrergic innervation.