Role of nitric oxide in nonadrenergic, noncholinergic relaxation of whole tracheal tube preparations isolated from guinea pigs.

1. Frequency-dependent nonadrenergic, noncholinergic (NANC) relaxant responses were induced by transmural stimulation of whole tracheal tube preparations. 2. Responses at lower frequencies (< or = 10 Hz) were abolished by L-nitroarginine methyl ester (L-NAME). 3. Responses at higher frequencies (> or = 20 Hz) consisted of a rapid, short-lasting relaxation, followed by a slow, long-lasting relaxation. The former and the latter were reduced by L-NAME and alpha-chymotrypsin, respectively. 4. alpha-Chymotrypsin had little effect on the magnitude of NANC responses, but reduced the duration of responses at higher frequencies (> or = 20 Hz). 5. The results suggest that NANC relaxation of guinea pig trachea may be mediated primarily by nitric oxide, with and without concomitant release of vasoactive intestinal peptide or related peptides, and nitric oxide may act as predominant mediator providing the magnitude of relaxant response.