The Role of the Superoxide Radical in the Regulation of the K<sub>V</sub>-Channels Function in the Coronary Vessels Following Posttraumatic Stress Disorder

Abstract

The purpose of the research was to study the contribution of the superoxide radical (\({\text{O}}_{2}^{{\centerdot - }}\)) to the mechanisms of the coronary KV-channels functional activity impairment 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 analogue of PTSD, the modified model of “a predator presence imitation” was applied (contact with cats’ excrements for 10 days, 15 minutes daily). The PTSD development was confirmed by behavioral changes of affected animals in the “Open Field” test. The coronary vessels’ tone was studied on the isolated by the Langendorf’s method isotonically contracted hearts, which were perfused under constant flow with Krebs–Henseleit solution. The contribution of \({\text{O}}_{2}^{{\centerdot - }}\) to the coronary vascular tone regulation was studied by infusion of the superoxide radical “scavenger” Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) in the perfusion solution. The functional activity of KV-channels was assessed by the degree of increase in the coronary perfusion pressure (CPP) in response to 4-aminopyridine (4-AP), a blocker of KV-channels. To elucidate the role of \({\text{O}}_{2}^{{\centerdot - }}\) in the KV‑channels functional activity of coronary vessels, Tiron and 4-AP were infused in the perfusion solution. The concentration of diene conjugates (DCs), malondialdehyde (MDA), C‑reactive protein (C-RP) and interleukin 1β (IL-1β) as well as catalase (CAT) and superoxide dismutase (SOD) activity were detected in the blood serum of experimental animals. The CPP in the isolated rats’ hearts after PTSD was 30% lower at coronary flow rate 10 mL/min compared to the control group. Under the influence of 4-AP, CPP increased by 70% and by 24% in the “Control” and “PTSD” groups, respectively. Under influence of Tiron, the CPP in the “PTSD” group at coronary flow rate 10 mL/min was 52% lower than in the control. In the “PTSD + Tiron + 4-AP” group the CPP augmentation (71.5%) was comparable to that in the hearts of the “Control” group after 4-AP exposure. The IL-1β, C-RP, DCs and MDA concentration in the blood serum of rats with PTSD was 3, 1.6, 3.3 and 3.6 times higher than in the control rats’ blood serum, while SOD and CAT activity was by 27 and 59% lower, compared to control, respectively. In the course of the investigation, it was found that \({\text{O}}_{2}^{{\centerdot - }}\) overproduction due to oxidative stress might be an important mechanism of a poststressor “channelopathy”, which is characterized by the decreased functional activity of the KV-channels of coronary vessels following PTSD.