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Carbon Monoxide Induces Dose‐Dependent Relaxation of Airway Smooth Muscle via cGMP Signaling Pathway
Author(s) -
Jakupaj Muharrem,
Lajçi Azem,
Bexheti Sadi,
Temaj Gazmend,
Cenaj Asllan,
Sopi Ramadan B
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb876
Subject(s) - nitric oxide , chemistry , heme , soluble guanylyl cyclase , nitric oxide synthase , heme oxygenase , muscle relaxation , stimulation , pharmacology , carbon monoxide , biochemistry , biophysics , enzyme , endocrinology , guanylate cyclase , medicine , biology , organic chemistry , catalysis
In present study we investigated the effect of endogenous carbon monoxide (CO) on relaxation of rat airway smooth muscle (ASM). Airway segments were excised from 28 day‐old rats. In pre‐constricted tracheal smooth muscle (TSM), electrical field stimulation (EFS) was applied to induce relaxation in absence or presence of heme oxigenase (HO) substrate ‐ hematin (10 μM and 100 μM); HO inhibitor tin protoporphyrin‐IX (SnPP‐IX; 100 μM); nitric oxide (NO) synthase (NOS) inhibitor N ω ‐nitro‐L‐arginine methyl ester (L‐NAME; 100 μM); soluble guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ; 10 μM) and the SnPP‐IX + L‐NAME. All experiments were performed in presence of isoproterenol (100 μM) and indomethacin. Hematin increased relaxant responses of ASM in a dose‐dependent manner. SnPP‐IX and L‐NAME, alone or combined significantly reduced relaxant responses induced by EFS in control and hematin‐preincubated tissues. ODQ also reduced relaxant responses to the level obtained by combining SnPP‐IX and L‐NAME. According to the results we conclude that in rat TSM, CO induces dose‐dependent relaxation and nondrenergic noncholinergic (NANC) inhibitory responses use CO and NO as main molecules to induce relaxation via cGMP signaling pathway.