Inhibition byl-NG-Nitro-l-Arginine of Nonadrenergic-Noncholinergic-mediated Relaxations of Human Isolated Central and Peripheral Airways

Abstract

Human isolated central (5 to 12 mm) and peripheral (< 2 mm) bronchi were contracted with 3 µM histamine. Relaxations were then evoked by electrical field stimulation (EFS) (1 to 32 Hz, 1 ms, 12 V for 15 s in the presence of indomethacin, atropine, and propranolol). The magnitude, time-course, and frequency-response relationship of these nonadrenergic, noncholinergic (NANC) relaxations were similar in the central and the peripheral airways. N^G-Nitro-l-arginine (l-NOARG) (10 µM) inhibited the tetrodotoxin-sensitive NANC relaxations in both central and peripheral bronchi, whereas the stereoisomer d-NOARG was without effect. This inhibition was reversed by l-arginine (1 mM) but not be d-arginine (1 mM). The nitric oxide donor compound, 3-morpholinosydnonimine (SIN-1), was equipotent at relaxing the central and peripheral airways. Vasoactive intestinal peptide (VIP), although it relaxed central airways, was virtually ineffective in relaxing the peripheral airways. In addition, the peptidase, α-chymotrypsin, at a concentration that blocked relaxations to VIP, was without effect on NANC relaxations in the central bronchi. The results support the following hypotheses: (1) both central and peripheral airways receive nonadrenergic relaxant innervation; (2) the relaxant response to electrical stimulation of this system is dependent on a pathway involving l-arginine; and (3) the relaxant response does not appear to involve VIP, but it may involve the production of nitric oxide.