Premium
Cytochrome P450 2C9 contributes to pulmonary vasoconstriction in exercising swine
Author(s) -
Zhou Zhichao,
Beer Vincent J,
Duncker Dirk J,
Merkus Daphne
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.898.1
Subject(s) - bradykinin , vasodilation , hypoxic pulmonary vasoconstriction , pharmacology , nitric oxide synthase , vasoconstriction , nitric oxide , medicine , chemistry , blockade , cyclooxygenase , endocrinology , biochemistry , enzyme , receptor
The role of endothelium‐derived hyperpolarizing factor (EDHF) in the pulmonary circulation, particularly the involvement of cytochrome P‐450 (CYP) 2C9 as an EDHF to regulate pulmonary vascular tone is incompletely understood. We investigated the contribution of CYP 2C9 to regulation of pulmonary vascular tone in swine at rest/during treadmill exercise. Inhibition of CYP 2C9 with sulfaphenazole had no effect on the systemic and pulmonary circulations either at rest or during exercise. Surprisingly, after blockade of both nitric oxide synthase (NOS) and cyclooxygenase (COX) with N‐nitro‐L‐arginine and indomethacin, sulfaphenazole produced significant systemic and pulmonary vasodilation, indicating a CYP 2C9‐mediated vasoconstrictor influence in these vascular beds both at rest and during exercise. In isolated pulmonary small arteries mounted on wire myograph, sulfaphenazole had no effect on the vasodilation produced by bradykinin under control conditions, but markedly enhanced the bradykinin‐induced vasodilation after pretreatment with NOS/COX blockade. The latter effect was no longer observed after pretreatment with reactive oxygen species (ROS) scavenger MPG. In conclusion, under basal conditions, CYP 2C9 is not critical for the regulation of pulmonary vascular tone either at rest or during exercise, but exerts a vasoconstrictor influence after NOS/COX blockade that appears ROS mediated.