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American journal of physiology. Heart and circulatory physiology, 1998-10, Vol.275 (4), p.H1283
Ort / Verlag
United States
Erscheinungsjahr
1998
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ）
Beschreibungen/Notizen
Department of Physiology and Biophysics, Wright State University
School of Medicine, Dayton, Ohio 45435
It has been known for a number of years that
neutrophils and macrophages secrete
H 2 O 2
while fighting disease, and the levels obtained within the vasculature
under these conditions can reach several hundred micromolar. Because
the effect of
H 2 O 2
on vascular smooth muscle is not fully understood, the present study
examined the cellular effects of
H 2 O 2
on coronary arteries. Under normal ionic conditions,
H 2 O 2
relaxed arteries that were precontracted with prostaglandin
F 2 or histamine
(EC 50 = 252 ± 22 µM). The
effect of
H 2 O 2
was concentration dependent and endothelium independent. In contrast,
H 2 O 2
did not relax arteries contracted with 80 mM KCl, suggesting
involvement of K + channels.
Single-channel patch-clamp recordings revealed that H 2 O 2
increased the activity of the large-conductance (119 pS), Ca 2+ - and voltage-activated
K +
(BK Ca ) channel. This response
was mimicked by arachidonic acid and inhibited by eicosatriynoic acid,
a lipoxygenase blocker, suggesting involvement of leukotrienes. Further
studies on intact arteries demonstrated that eicosatriynoic acid not
only blocked the vasodilatory response to
H 2 O 2
but unmasked a vasoconstrictor effect that was reversed by blocking
cyclooxygenase activity with indomethacin. These findings identify a
novel effector molecule, the BK Ca
channel, which appears to mediate the vasodilatory effect of
H 2 O 2 ,
and suggest that a single signaling pathway, arachidonic acid
metabolism, can mediate the vasodilatory and vasoconstrictor effects of
H 2 O 2
and possibly other reactive oxygen species.
lipoxygenase; cyclooxygenase