Inhibition of non-adrenergic non-cholinergic relaxations by nitric oxide donors. 1995

J G De Man, and G E Boeckxstaens, and B Y De Winter, and T G Moreels, and A G Herman, and P A Pelckmans
Division of Gastroenterology, University of Antwerp, Faculty of Medicine, Antwerp, Belgium.

The effects of pretreatment with the nitric oxide (NO)-releasing substances 3-morpholino-sydnoninime (SIN-1) and nitroglycerin were investigated on relaxations induced by non-adrenergic non-cholinergic (NANC) nerve stimulation, authentic NO and vasoactive intestinal polypeptide (VIP) in the rat gastric fundus. Short periods of electrical stimulation (0.5-16 Hz, 1 ms, pulse trains of 10 s) induced frequency-dependent transient relaxations, previously shown to be mainly mediated by NO. Both SIN-1 (10-100 microM) and nitroglycerin (0.5 mM) pretreatment significantly reduced these electrically induced responses to a similar extent as the inhibitor of the NO biosynthesis L-nitroarginine (30-300 microM). Prolonged periods of electrical stimulation (16 Hz, 1 ms, pulse trains of 180 s) induced a sustained relaxation, previously shown to be mediated by NO and VIP. L-Nitroarginine (30-300 microM) or pretreatment with SIN-1 (100 microM) or nitroglycerin (0.5 mM) did not affect the amplitude of this relaxation but slowed down its onset. Authentic NO (0.01-10 microM) and VIP (0.01-10 nM) induced respectively transient and sustained concentration-dependent relaxations. SIN-1 or nitroglycerin pretreatment had no effect on the concentration-response curves to NO and VIP. These results indicate that prolonged exposure to NO donors inhibits electrically induced nerve-mediated NANC relaxations without affecting the postjunctional response to NO and VIP. As similar results are obtained with NO biosynthesis inhibitors, our results illustrate a prejunctional inhibitory effect of NO on the NANC nerves of the rat gastric fundus and suggest the presence of an autoregulatory mechanism for the nitrergic innervation.

UI MeSH Term Description Entries
D007537 Isometric Contraction Muscular contractions characterized by increase in tension without change in length. Contraction, Isometric,Contractions, Isometric,Isometric Contractions
D008297 Male Males
D008981 Molsidomine A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS. Morsydomine,Corpea,Corvaton,Duracoron,Fali-Cor,Korvatone,MTW-Molsidomin,Molsi 1A Pharma,Molsi-AZU,Molsi-Puren,Molsibeta,Molsicor,Molsidain,Molsidomin,Molsidomin Heumann,Molsidomin Stada,Molsidomin Von Ct,Molsidomin-Ratiopharm,Molsihexal,Molsiket,SIN-10,Sydnopharm,Fali Cor,Heumann, Molsidomin,MTW Molsidomin,Molsi AZU,Molsi Puren,Molsidomin Ratiopharm,SIN 10,SIN10,Von Ct, Molsidomin
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005246 Feedback A mechanism of communication within a system in that the input signal generates an output response which returns to influence the continued activity or productivity of that system. Feedbacks
D005748 Gastric Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Fundus, Gastric
D005996 Nitroglycerin A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives. Glyceryl Trinitrate,Anginine,Dynamite,Gilustenon,Nitrangin,Nitro-Bid,Nitro-Dur,Nitrocard,Nitroderm,Nitroderm TTS,Nitroglyn,Nitrol,Nitrolan,Nitrong,Nitrospan,Nitrostat,Perlinganit,Susadrin,Sustac,Sustak,Sustonit,Transderm Nitro,Tridil,Trinitrin,Trinitrolong,Nitro Bid,Nitro Dur,NitroBid,NitroDur,Trinitrate, Glyceryl

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