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

Abstract

1 We examined the effect of variations in resting smooth-muscle tone induced by 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 gM atropine, 1IOM guanethidine) to electrical field stimulation (1200 mA; 0.5 ms; 240s; 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 (10pM), or the leukotriene receptor antagonist, FPL 55712 (11.5 gM), 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.

Non‐adrenergic, non‐cholinergic neural activation in guinea‐pig bronchi: powerful and frequency‐dependent stabilizing effect on tone

“…Convergence effect This term was used as an estimation of the added power of the converging contractile and relaxant NANC responses (Linden et al, 1991b). The convergence effect was defined on the basis of the difference between the lowest (no histamine) and the highest level of tone (histamine 6ptM) established prior to NANC activation by EFS.…”

“…Stabilization level This term was used to designate the level towards which the contractile and relaxant NANC responses tended to adjust tone and describes the balance between these contractile and relaxant responses (Linden et al, 1991b). As mentioned above, three EFS were evoked within the same airway preparation, each at a different level of tone prior to stimulation.…”

“…Although this decay in passive tension was small, it proved to be statistically significant 4.0 (95% confidence interval for decay: 0.06-0.14 g, n = 4). (Linden et al, 1991b) also argues against the importance of any decay in passive tension. This is because we used a parallel experimental design in the referred study instead of the present sequential design (methods).…”

“…A recent study demonstrated that, depending on the level of smooth-muscle tone prior to activation, NANC activation evokes either a contraction or a relaxation, converging towards a similar tone level in the guinea-pig isolated trachea (Linden et al, 1991b). As indicated in vitro, NANC responses may thus counteract changes in tone and play a stabilizing role in the control of tone.…”

“…Constant current generators provided electrical field stimulation (EFS) via platinum electrodes mounted on opposite sides of the airway preparation (Linden et al, 1991b). Square biphasic electrical impulses of 0.5 ms duration were used for both control contractions (1200 mA, 12 Hz for 20 s) and NANC activation (300-1500 mA, 1, 3 and 10 Hz for 240 s).…”