Role of the Superoxide Radical in Regulation of Coronary Vascular Kv Channels in Posttraumatic Stress Disorder
Tóm tắt
The aim of this work was to study the contribution of the
superoxide radical (О2●–) to the mechanisms
underlying the dysfunction of coronary voltage-gated potassium (Kv)
channels in rats with posttraumatic stress disorder (PTSD). The
study was performed on 117 outbred white male rats Rattus muridae weighing 210–240 g.
To reproduce the experimental PTSD analog, a modified predator presence
simulation model was used (contact with cat feces for 10 days, 15
min daily). PTSD development was confirmed by behavioral changes
of affected animals in the Open Field test. Coronary vascular tone
was studied on the isolated, isotonically contracting Langendorff rat
hearts continuously perfused with a Krebs-Henseleit solution. O2
●– contribution
to coronary vascular tone regulation was studied by adding its scavenger,
Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid), to a perfusion
solution. The functional activity of Kv channels
was assessed by the degree of increment in coronary perfusion pressure
(CPP) in response to 4-aminopyridine (4-AP), a Kv channel
blocker, also added to a perfusion solution. In rat blood serum,
the levels of diene conjugates (DCs) and malondialdehyde (MDA),
as well as catalase (CAT) and superoxide dismutase (SOD) activities,
were determined by spectrophotometry, while C-reactive protein (CRP)
and interleukin 1β (IL-1β) levels were assayed by immunoenzyme analysis.
In isolated hearts of PTSD rats (PTSD group), at a constant volume
flow rate (CVFR) of 10 mL/min, CPP was 30% lower than in the Control
group. 4-AP increased CPP by 24% in the PTSD group and by 70% in
the Control group. After Tiron addition to a perfusion solution,
at the same CVFR of 10 mL/min, CPP in the PTSD group was 52% lower
compared to the Control group. In the PTSD + Tiron + 4-AP group,
4-AP-induced CPP increment (71.5%) was comparable to that in the
Control group. In PTSD rats, IL-1β, CRP, DC and MDA serum levels were,
respectively, 3, 1.6, 3.3 and 3.6 times higher than in control rats,
while SOD and CAT activities were, respectively, 27 and 59% lower
than in control animals. Thus, it was found that in PTSD rats, the
functional activity of coronary vascular Kv channels
is reduced, with oxidative stress-induced O2
●– overproduction
being one of the key putative mechanisms of such a channelopathy.
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