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Mechanism of hydrogen sulfide mediated contraction in rat small pulmonary arteries
Author(s) -
Aaronson Philip Irving,
Prieto-Lloret Jesus,
Snetkov Vladimir,
Connolly Michelle,
Ward Jeremy
Publication year - 2012
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.26.1_supplement.871.5
Subject(s) - chemistry , contraction (grammar) , biophysics , antimycin a , sulfide , reactive oxygen species , hyperpolarization (physics) , mitochondrion , medicine , biochemistry , stereochemistry , biology , organic chemistry , nuclear magnetic resonance spectroscopy
The gas H 2 S (sulfide) causes a biphasic contraction of unknown mechanism in pulmonary arteries (PA). We assessed this mechanism in rings of rat 2 nd order PA using myography to measure tension and NaHS as a source of sulfide. Reactive oxygen species (ROS) levels and the mitochondrial membrane potential (Δψ) were recorded using the indicators LO12 and TMRE, respectively. NaHS (500μM) evoked a small contraction and then a much larger 2 nd contraction which gradually relaxed. The 2 nd contraction was strongly reduced by 10μg/ml antimycin (AM) and 50μM dantrolene but was unaffected by 1μM rotenone (ROT). 10 or 30μM sulfide caused an immediate transient rise in [ROS]; at 100–1000μM this was followed by a 2 nd larger rise in ROS which fell to baseline within ~10 min. The biphasic increases in tension and ROS had similar timecourses. The rise in [ROS] was slightly blocked by 1μM ROT but was almost abolished by 10μg/ml AM. 500 μM sulphide caused a triphasic effect on Δψ: a rapid very transient hyperpolarization was followed by a depolarization, a 2 nd slower hyperpolarization, and then a return to baseline. Sulfide oxidation by the mitochondrial flavoprotein sulfide‐quinone oxoreductase (SQR), which is expressed in PA, has been shown in some cells to generate electrons that are passed to complex 3. We propose that metabolism of sulfide by SQR gives rise to a complex 3‐mediated increase in ROS that causes a contraction by activating the RyR.