Role of NO in vagally-mediated relaxations of guinea-pig stomach.
Vagal stimulation of the stomach induces a relaxation mediated via non-adrenergic, non-cholinergic (NANC) nerves. The neurotransmitter which is responsible for this relaxation is still unknown. To determine whether nitric oxide (NO) or a NO related substance mediates this relaxation, an intact guinea-pig stomach was mounted in an organ bath, with electrodes surrounding the vagal nerves. Electrical stimulation of the vagal nerves, in the presence of atropine, induced frequency dependent, tetrodotoxin-(TTX) sensitive relaxations of the stomach quantified as changes in volume. These relaxations were not affected by alpha- or beta-adrenoceptor antagonists or guanethidine. Thus they were evoked by non-adrenergic, non-cholinergic (NANC) inhibitory nerves. The relaxant responses could be inhibited in a concentration-dependent manner by NG-nitro-L-arginine (L-NNA) a substance that inhibits the formation of nitric oxide (NO). Addition of L-arginine, the substrate for NO-synthase, reversed the L-NNA-induced-inhibition of the relaxation. Addition of nitroglycerin (a NO-donor) to a non-stimulated stomach mimicked the relaxations observed after vagal stimulation in a concentration dependent manner. These relaxations were insensitive to TTX. Relaxation of the stomach by vagal stimulation was prevented by an inhibitor of soluble guanylate cyclase, methylene blue, further supporting our conclusions. These data indicate that NO or a substance releasing NO plays an important role in NANC-neurotransmission after vagal stimulation of the guinea-pig stomach.
Meulemans
A L
AL
Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Helsen
L F
LF
Schuurkes
J A
JA
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000294:innervation*; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D001120:Arginine; D005996:Nitroglycerin; D008751:Methylene Blue