AIM:To test whether high-frequency electrical stimulation(HES)of the bilateral cervical vagus nerves reduces the airway responses to methacholine(MCh).METHODS:Guinea pigs were pretreated with saline(Sal,n=9)or ovalbumin(Ova,n=10)aerosol for two weeks(5 min/d,5 d/wk)and subsequently anesthetized,paralyzed,tracheotomized and artificially ventilated.Both total lung resistance(RL)and dynamic pulmonary compliance(Cdyn)were recorded.In addition,the effects of vagal low-frequency electrical stimulation(LES,monophasic,50 Hz)and HES(monophasic and biphasic,1 and 2.5 kHz)for about 10 s or 2 min on the responses of RL and Cdyn to MCh aerosol-induced bronchoconstriction were compared in both groups of guinea pigs.In a few guinea pigs,the impact of bivagotomy on the RL responses to MCh was assessed.RESULTS:Before MCh challenge,LES,but not HES,significantly increased RL by about 30%(P<0.01)and decreased Cdyn by about 20%(P<0.01)similarly in both groups.MCh aerosol for 2 min elevated RL and diminished Cdyn more in Ova-than Sal-treated animals(RL:313%±52%vs 113%±17%,P<0.01;Cdyn:-56%±7%vs-21%±3%,P<0.01).During MCh-induced airway constriction,LES further enhanced,but HES decreased RL and this decrease was greater in Ova-(about 45%)than Sal-treated animals(about 34%,P<0.01)with little change in cardiovascular activity.On the other hand,LES further reduced whereas HES increased Cdyn more in Ova-(about 20%)than Sal-treated animals(about 13%,P<0.01).In addition,bivagotomy almost eliminated the RL and Cdyn responses to MCh.CONCLUSION:We conclude that vagal HES is able to alleviate the bronchoconstriction induced by MCh in anesthetized guinea pigs,likely via reversible inhibition/blockade of vagal conduction.