Hypoxic conditioning suppresses cytotoxic nitricoxide production by endothelium upon reperfusion following acute myocardial ischemia

ИШЕМИИ ПРЕРЫВИСТОЙ ФЕНОМЕНИШЕМИЧЕСКАЯ БОЛЕЗНЬ СЕРДЦАСЕРДЦА БОЛЕЗНИЦИТОТОКСИНЫ /ВРЕД ВОЗДАЗОТА ОКСИДЫЭНДОТЕЛИЙ /ПОВРЕЖДМИОКАРДА РЕПЕРФУЗИОННЫЕ ПОВРЕЖДЕНИЯРЕПЕРФУЗИОННОЕ ПОВРЕЖДЕНИ

Normobaric hypoxia conditioning reduces blood pressure and normalizes nitric oxide synthesis in patients with arterial hypertension

,d Objectives Insufficient production and/or increased decomposition of the potent endogenous vasodilator nitric oxide plays an important role in development and progression of arterial hypertension and its complications. One of the most effective means of stimulating endogenous nitric oxide synthesis is controlled adaptation to hypoxia. This study examined the effect of a 20-day, intermittent, normobaric intermittent hypoxia conditioning (IHC) program on blood pressure (BP) and nitric oxide production in patients with stage 1 arterial hypertension. Methods The IHC sessions consisted of four to 10 cycles of alternating 3-min hypoxia (10% FIO 2 ) and 3-min room air breathing. BP was monitored for 24 h before and after IHC, and nitric oxide synthesis was evaluated by 24-h urinary excretion of the stable nitric oxide metabolites nitrate and nitrite. Results IHC increased nitric oxide synthesis and decreased BP in hypertensive patients to values similar to those of normotensive individuals. Significant inverse correlations were found between nitric oxide production and disease duration, SBP, and DBP. Moreover, IHC enhancement of nitric oxide synthesis was especially robust in patients with arterial hypertension of more than 5 years duration. The reduction in BP persisted for at least 3 months in 28 of 33 hypertensive patients. Conclusion IHC exerted a robust, persistent therapeutic effect and can be considered as an alternative, nonpharmacological treatment for patients with stage 1 arterial hypertension. The antihypertensive action of IHC is associated with normalization of nitric oxide production

Mechanisms of Susceptibility and Resilience to PTSD: Role of Dopamine Metabolism and BDNF Expression in the Hippocampus

Susceptibility and resilience to post-traumatic stress disorder (PTSD) are recognized, but their mechanisms are not understood. Here, the hexobarbital sleep test (HST) was used to elucidate mechanisms of PTSD resilience or susceptibility. A HST was performed in rats 30 days prior to further experimentation. Based on the HST, the rats were divided into groups: (1) fast metabolizers (FM; sleep duration < 15 min); (2) slow metabolizers (SM; sleep duration ≥ 15 min). Then the SM and FM groups were subdivided into stressed (10 days predator scent, 15 days rest) and unstressed subgroups. Among stressed animals, only SMs developed experimental PTSD, and had higher plasma corticosterone (CORT) than stressed FMs. Thus, resilience or susceptibility to PTSD was consistent with changes in glucocorticoid metabolism. Stressed SMs had a pronounced decrease in hippocampal dopamine associated with increased expressions of catecholamine-O-methyl-transferase and DA transporter. In stressed SMs, a decrease in monoaminoxidase (MAO) A was associated with increased expressions of hippocampal MAO-A and MAO-B. BDNF gene expression was increased in stressed FMs and decreased in stressed SMs. These results demonstrate relationships between the microsomal oxidation phenotype, CORT concentration, and anxiety, and they help further the understanding of the role of the liver–brain axis during PTSD

Cerebral Blood Flow in Predator Stress-Resilient and -Susceptible Rats and Mechanisms of Resilience

Stress-induced conditions are associated with impaired cerebral blood flow (CBF) and increased risk of dementia and stroke. However, these conditions do not develop in resilient humans and animals. Here the effects of predator stress (PS, cat urine scent, ten days) on CBF and mechanisms of CBF regulation were compared in PS-susceptible (PSs) and PS-resilient (PSr) rats. Fourteen days post-stress, the rats were segregated into PSs and PSr groups based on a behavior-related anxiety index (AI). CBF and its endothelium-dependent changes were measured in the parietal cortex by laser Doppler flowmetry. The major findings are: (1) PS susceptibility was associated with reduced basal CBF and endothelial dysfunction. In PSr rats, the basal CBF was higher, and endothelial dysfunction was attenuated. (2) CBF was inversely correlated with the AI of PS-exposed rats. (3) Endothelial dysfunction was associated with a decrease in eNOS mRNA in PSs rats compared to the PSr and control rats. (4) Brain dopamine was reduced in PSs rats and increased in PSr rats. (5) Plasma corticosterone of PSs was reduced compared to PSr and control rats. (6) A hypercoagulation state was present in PSs rats but not in PSr rats. Thus, potential stress resilience mechanisms that are protective for CBF were identified

Unveiling the Link: Exploring Mitochondrial Dysfunction as a Probable Mechanism of Hepatic Damage in Post-Traumatic Stress Syndrome

PTSD is associated with disturbed hepatic morphology and metabolism. Neuronal mitochondrial dysfunction is considered a subcellular determinant of PTSD, but a link between hepatic mitochondrial dysfunction and hepatic damage in PTSD has not been demonstrated. Thus, the effects of experimental PTSD on the livers of high anxiety (HA) and low anxiety (LA) rats were compared, and mitochondrial determinants underlying the difference in their hepatic damage were investigated. Rats were exposed to predator stress for 10 days. Then, 14 days post-stress, the rats were evaluated with an elevated plus maze and assigned to HA and LA groups according to their anxiety index. Experimental PTSD caused dystrophic changes in hepatocytes of HA rats and hepatocellular damage evident by increased plasma ALT and AST activities. Mitochondrial dysfunction was evident as a predominance of small-size mitochondria in HA rats, which was positively correlated with anxiety index, activities of plasma transaminases, hepatic lipids, and negatively correlated with hepatic glycogen. In contrast, LA rats had a predominance of medium-sized mitochondria. Thus, we show links between mitochondrial dysfunction, hepatic damage, and heightened anxiety in PTSD rats. These results will provide a foundation for future research on the role of hepatic dysfunction in PTSD pathogenesis