Non-adrenergic, non-cholinergic neural activation stabilizes smooth-muscle tone independently of eicosanoid factors in guinea-pig isolated airways.

1. We examined the effect of variations in resting smooth-muscle tone induced eicosanoid inhibitors on the direction and magnitude of the non-adrenergic, non-cholinergic (NANC) nervous response in guinea-pig isolated airways. 2. NANC responses (in the presence of 1 microM atropine, 10 microM guanethidine) to electrical field stimulation (1200 mA; 0.5 ms; 240 s; 3 Hz) were studied in guinea-pig isolated airway preparations (n = 4-7) taken from the proximal trachea, the distal trachea and the main bronchus. Tissues were treated with either the cyclo-oxygenase-blocker, indomethacin (10 microM), or the leukotriene receptor antagonist, FPL 55712 (11.5 microM), to modulate the resting tone. 3. Depending on the level of resting tone prior to electrical field stimulation, NANC activation induced either a contraction or a relaxation converging towards a similar level of tone, a 'tonus equilibrium'. This tonus equilibrium displayed an increasing level towards the periphery (3 +/- 3 (s.e.mean) % for the proximal trachea, 28 +/- 3% for the distal trachea and 54 +/- 4% for the main bronchus, in % of maximum active tension). After NANC activation, the tonus returned to a level similar to the resting tone. 4. We conclude that changes in resting smooth-muscle tone not only affect the magnitude but also the direction of the NANC response. It is suggested that the NANC nervous system is a stabilizing factor in the regulation of airway smooth-muscle tone, independent of eicosanoid factors. An increasing contractile component and a decreasing relaxant component of the NANC system towards the peripheral airways is indicated.