In vitro characteristics of spontaneous airway tone in the guinea-pig.

Abstract

Spontaneous airway tone has been demonstrated in the guinea-pig and man in vitro but little data on the magnitude and time-course of this phenomenon is available. Moreover, the literature on possible mediators is conflicting. In the present in vitro study, spontaneous airway tone (measured as spontaneous active tension) was examined in frontally-opened guinea-pig airway rings (n = 4-8). The examination related to magnitude, time-course and segmental differences as well as the role of eicosanoids, acetylcholine and adrenergic mechanisms. Spontaneous active tension of considerable magnitude (approximately 40% of maximum active tension) and stability was recorded during the second hour of the experiments. An initial small segmental difference between the trachea and the main bronchus gradually decreased during the first hour of observation. Cyclooxygenase inhibition by indomethacin completely abolished the spontaneous active tension. The leukotriene antagonist FPL 55712 reduced the active tension, whereas the leukotriene antagonist L-648,051 did not significantly affect it. Muscarinic blockade and adrenergic depletion had no effect. We conclude that the spontaneous active tension is of such a large magnitude and stability that it may play an important role in maintaining normal airway tone and that there are no pronounced segmental differences. The complete inhibition by indomethacin and the lack of effect by L-648,051 indicate that the spontaneous airway tone is primarily maintained by prostanoids and suggest that leukotriene D4 is of minor importance. The effect of FPL 55712 was probably due to inhibition of phosphodiesterase.