Effects of nitric oxide on slow waves and spontaneous contraction of guinea pig gastric antral circular muscle

We examined the effects of nitric oxide (NO) donors, S-nitroso-L-cysteine (Cys-NO) and 3-morpholinosydnonimine hydrochloride (SIN-1), on slow waves and contractile activity in the circular muscle of guinea pig gastric antrum. In the presence of atropine and guanethidine, electrical field stimulation (EPS) reduced the amplitude of phasic contraction. The effect of EFS was significantly inhibited by both the NO synthase inhibitor N^ω-nitro-L-arginine methyl ester and a soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Cys-NO and SIN-1 mimicked the effect of EFS on phasic contraction and reduced the amplitude of slow waves in a concentration-dependent manner, with no effect on frequency and resting membrane potential. Phasic contraction was more sensitive to NO donors than slow waves. The inhibitory effects of NO donors were antagonized by ODQ and mimicked by a membrane permeable cGMP analogue 8-bromo-cGMP. Several K⁺ channel blockers such as apamin, iberiotoxin, and glibenclamide had no effect on the inhibitory action of SIN-1. These results suggest that NO inhibits the phasic contraction and slow waves through cGMP-dependent mechanisms in guinea pig gastric antrum. The effect of NO is unlikely to be mediated by the activation of Ca²⁺-activated or ATP-sensitive K⁺ channels.