Effect of molsidomine and linsidomine on the human isolated bronchus and the guinea-pig isolated trachea. 1993

Y Zhang, and C Palette-Pays, and E Naline, and O Varoquaux, and C Advenier
Faculté de Médecine Paris-Ouest, France.

The effects of molsidomine and its metabolite linsidomine were studied on the guinea-pig isolated trachea and on the human isolated bronchus. These effects were compared with those of nitrate derivatives (sodium nitroprusside, isosorbide dinitrate), theophylline, zardaverine and isoprenaline. Linsidomine exerted a relaxant effect similar to that of sodium nitroprusside on the two types of preparations precontracted with acetylcholine, histamine or potassium chloride. Molsidomine was about one-hundredth as potent as linsidomine, and less efficacious. The effects of the two substances were not modified by removal of the human bronchial epithelium. The concentration-response curves of linsidomine and sodium nitroprusside were significantly shifted to the right by methylene blue (3 x 10(-5) M) but the effects of isoprenaline were unmodified. The effects of linsidomine and sodium nitroprusside were potentiated specifically by zaprinast (10(-6)-10(-5) M), an inhibitor of type Ia or V phosphodiesterases, whereas the effects of isoprenaline were potentiated by zardaverine (10(-9)-10(-8) M), an inhibitor of class III and IV phosphodiesterases. The effects of all three substances (linsidomine, isoprenaline and sodium nitroprusside) were potentiated equally by theophylline (10(-5)-10(-4) M), a nonspecific inhibitor of phosphodiesterases. It is concluded that linsidomine is a potent relaxant of the smooth muscle of the guinea-pig isolated trachea and human isolated bronchus. In terms of potency and efficacy, its effect is much superior to that of the parent compound molsidomine. It is suggested that linsidomine acts, like nitrate derivatives, through the guanylate cyclase-cGMP system.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008297 Male Males
D008751 Methylene Blue A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN. Methylthionine Chloride,Swiss Blue,Basic Blue 9,Chromosmon,Methylene Blue N,Methylthioninium Chloride,Urolene Blue,Blue 9, Basic,Blue N, Methylene,Blue, Methylene,Blue, Swiss,Blue, Urolene
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
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
D009599 Nitroprusside A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. Nitroferricyanide,Sodium Nitroprusside,Cyanonitrosylferrate,Ketostix,Naniprus,Nipride,Nipruton,Nitriate,Nitropress,Nitroprussiat Fides,Nitroprusside, Disodium Salt,Nitroprusside, Disodium Salt, Dihydrate,Disodium Salt Nitroprusside,Nitroprusside, Sodium
D011688 Purinones Oxopurines
D011724 Pyridazines Six-membered rings with two adjacent nitrogen atoms also called 1,2-diazine.
D001980 Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI. Primary Bronchi,Primary Bronchus,Secondary Bronchi,Secondary Bronchus,Tertiary Bronchi,Tertiary Bronchus,Bronchi, Primary,Bronchi, Secondary,Bronchi, Tertiary,Bronchus,Bronchus, Primary,Bronchus, Secondary,Bronchus, Tertiary
D001993 Bronchodilator Agents Agents that cause an increase in the expansion of a bronchus or bronchial tubes. Bronchial-Dilating Agents,Bronchodilator,Bronchodilator Agent,Broncholytic Agent,Bronchodilator Effect,Bronchodilator Effects,Bronchodilators,Broncholytic Agents,Broncholytic Effect,Broncholytic Effects,Agent, Bronchodilator,Agent, Broncholytic,Agents, Bronchial-Dilating,Agents, Bronchodilator,Agents, Broncholytic,Bronchial Dilating Agents,Effect, Bronchodilator,Effect, Broncholytic,Effects, Bronchodilator,Effects, Broncholytic

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