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Low concentrations of reactive oxygen species cause vasoconstriction of small distal pulmonary arteries.
Author(s) -
Pourmahram Ghazaleh Esmaeil,
Becker Silke,
Aaronson Philip I,
Ward Jeremy PT
Publication year - 2006
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.20.5.a1229-b
Subject(s) - hypoxic pulmonary vasoconstriction , constriction , vasoconstriction , reactive oxygen species , menadione , chemistry , hypoxia (environmental) , mitochondrial ros , oxygen , blockade , medicine , endocrinology , biophysics , biology , biochemistry , oxidative stress , receptor , organic chemistry
Controversy rages as to the role of mitochondria‐derived reactive oxygen species (ROS) in hypoxic pulmonary vasoconstriction. As a basic premise, exogenous ROS should mimic hypoxia if an elevation in ROS underlies HPV, but cause dilatation (or do nothing) if HPV is initiated by a fall in ROS. Although H 2 O 2 has been shown to constrict pulmonary artery, this was for concentrations far higher (mM) than physiological levels. We therefore examined low concentrations of H 2 O 2 and menadione, which increases ROS generation primarily by mitochondria, on rat small intrapulmonary arteries (IPA). 10–100μM H 2 O 2 caused vasoconstriction, with a large transient and small sustained component. At 30μM H 2 O 2 the transient was 10 ± 3% of 80mM KCl induced tension (KPSS), and the sustained constriction 4 ± 1% (n=11). Menadione caused a sustained constriction, reaching 6 ± 3% KPSS at 8μM (n=5). These constrictions are small, but HPV is potentiated by pretone. We therefore examined this for H 2 O 2 and menadione. Pretone (~15% KPSS) induced by 27mM [K + ] significantly potentiated H 2 O 2 ‐induced transient constrictions (to 51 ± 7% KPSS, n=7, p<0.001), and induced by PGF 2α significantly potentiated menadione‐induced constriction (47 ± 4% KPSS, n=8, p<0.001). Constriction to either agent was only partially suppressed by blockade of Ca 2+ entry pathways. Constriction induced by ROS thus shows some similarities to HPV. Whilst only providing circumstantial evidence that a rise in ROS might underlie HPV, these results predicate against the concept of a fall in ROS generation being the primary initiator of HPV. Funded by the British Heart Foundation