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Hematin Supplementation Reverses the Impaired Airway Relaxation in Neonatal Rats Exposed to Hyperoxia
Author(s) -
Sopi Ramadan B,
Zaidi Syed IA,
Bexheti Sadi,
Temaj Gazmend,
Lajçi Azem,
Jakupaj Muharrem
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.lb881
Subject(s) - hyperoxia , chemistry , stimulation , heme , muscle relaxation , endocrinology , respiratory system , pharmacology , medicine , biochemistry , lung , enzyme
It was shown that hyperoxia reduces nonadrenergic noncholinergic relaxation of airway smooth muscle (ASM). Therefore, we hypothesize that increase of carbon monoxide (CO) production by supplementation of tissues with hematin will reverse the hyperoxia‐induced impaired relaxant responses. Tracheal rings were excised from rat pups 12 days old, exposed to hyperoxia or room air for seven days. In pre‐constricted tracheal smooth muscle (TSM), electrical field stimulation (EFS) was applied to induce relaxation. The preparations were supplemented with heme oxigenase (HO) substrate ‐ hematin in presence or absence of HO inhibitor tin protoporphyrin‐IX (SnPP‐IX; 100 μM), and/or soluble guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a] quinoxalin‐ 1‐one (ODQ; 10 μM). In hyperoxic animals the relaxant responses were decreased significantly, but supplementation of tissues with hematin reversed these impaired relaxation. Inhibiton of HO by SnPP‐IX diminished this effect of hematin, whereas inhibition of guanylyl cyclase by ODQ alone or in combination with SnPP‐IX nearly abolished relaxant responses. We conclude that increase of CO production reverses the hyperoxia‐induced impaired relaxation and this may serve as a therapeutic approach in treatment of conditions characterized with airway hyperreactivity.