Sodium azide induces relaxation of the canine gastric body by activating a guanylate cyclase-dependent pathway.
In order to study the inhibitory mechanism by which sodium azide eliminates smooth muscle contraction in vivo and in vitro, gastrointestinal motility was monitored via chronically implanted force transducers in the stomach and duodenum of conscious dogs. Circular smooth muscle strips with myenteric plexus from the canine gastric body were used for in vitro measurement of isometric tension. In conscious dogs, sodium azide (50 micrograms kg-1, i.v.) abolished both the spontaneously occurring phase III contractions and postprandial motility. Exogenous motilin (100 ng kg-1)- and bethanechol (50 micrograms kg-1)-induced contractions were also abolished by sodium azide. In vitro, sodium azide and electrical field stimulation (EFS) caused a concentration- or frequency-dependent nonadrenergic noncholinergic relaxation in the gastric body strips. The relaxation induced by EFS, but not sodium azide, was abolished by tetrodotoxin. NG-nitro-L-arginine and oxyhaemoglobin failed to attenuate the relaxant effect of sodium azide, but strongly inhibited EFS-induced relaxation. Methylene blue inhibited both sodium azide- and EFS-induced relaxation. cGMP concentrations in muscle strips were markedly increased by sodium azide. These findings indicate that sodium azide induces relaxation in the canine gastric body through a direct action on smooth muscle, by activating a guanylate cyclase-dependent pathway; endogenous NO synthesis does not participate in this inhibitory mechanism.
Sano
I
I
Gastrointestinal Research Laboratories, Gunma University, Maebashi, Japan.
Mizumoto
A
A
Sakai
T
T
Tamura
T
T
Itoh
Z
Z
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology*; D009569:Nitric Oxide / Q000502:physiology; D010646:Phentolamine / Q000494:pharmacology; D019518:Postprandial Period / Q000502:physiology; D019810:Sodium Azide / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects* / Q000201:enzymology*
D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019810:Sodium Azide; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D010646:Phentolamine