Inhibition of airway smooth muscle tone by Chinese herbal medicines

The aim of the present study was to elucidate whether Chinese traditional h erbal drugs, Gorei-San (TJ-17) and Toki-Shakuyaku-San (TJ-23), affect airwa y smooth muscle tone and, if so, to determine what the mechanism of action is. Rabbit tracheal segments were isolated and the contractile responses to ele ctrical field stimulation and acetylcholine were measured before and after the application of TJ-17 or TJ-23 under isometric conditions in vitro. Ouab ain-sensitive rubidium-86 (Rb-86) uptake by tissues in response to each dru g was also measured. Each herbal medicine attenuated the contractile responses to electrical fie ld stimulation and acetylcholine in a concentration-dependent manner, the m aximal inhibition of acetylcholine-induced contraction being 37.5+/-4.9% fo r TJ-17 and 42.4+/-5.3% for TJ-23 (p<0.05 for each). These effects were not altered by mechanical removal of the epithelium, indomethacin, the nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester, the cyclic aden osine monophosphate (cAMP)-dependent protein kinase inhibitor adenosine 3'5 '-cyclic monophosphorothioate (Rp-cAMPS), the cyclic guanosine monophosphat e (cGMP)-dependent protein kinase inhibitor KT5823, or the calcium (Ca2+)-a ctivated potassium (K+) channel inhibitor charybdotoxin, but were greatly i nhibited in the presence of the sodium (Na+)-K+ adenosine triphosphatase (A TPase) inhibitor ouabain. Incubation of tissues with TJ-17 and TJ-23 dose d ependently increased ouabain-sensitive Rb-86 uptake. The results of the study suggest that both Gorei-San and Toki-Shakuyaku-San reduce airway smooth muscle tone via a postjunctional mechanism probably t hrough stimulation of the sodium pump and the subsequent hyperpolarization/ repolarization of the cell membrane. These effects may contribute to the an tiasthmatic properties of these herbal medicines.