Time-Dependent Production of Endothelium-Related Biomarkers is Affected Differently in Hemorrhagic and Septic Shocks

Demirel-Yilmaz, Emine/0000-0002-2476-6225; Usanmaz, Suzan E./0000-0002-7096-1347WOS: 000419896200004PubMed: 29019070Shock is associated with inflammation-induced endothelial dysfunction. The aim of this study was to determine time-dependent alteration of blood biomarkers related to endothelial function in hemorrhagic and septic shocks. Hemorrhagic shock was induced by bleeding the animals. A cecal ligation and incision model was used to induce septicemia. Resuscitation was carried out by infusion of lactated Ringer's solution. Resuscitation extended survival time in both shock groups. Blood pressure increased by resuscitation in the hemorrhagic shock but not in the septic shock. While hemorrhage caused a decrease in plasma levels of nitric oxide (NO) and hydrogen sulfide (H2S), asymmetric dimethylarginine (ADMA) and total antioxidant capacity (TAC) levels were increased. Only NO and TAC levels at the late phase were reversed by resuscitation. On the other hand, plasma levels of NO, ADMA, and TAC were increased by septicemia and resuscitation did not alter the septicemia-induced increase. These results indicate that blood biomarkers related to endothelial function were differentially affected by hemorrhage and septicemia. The time scale of biomarker production should be taken into consideration for the diagnostic and therapeutic approaches to these life-threatening diseases.Commission of the Scientific Research Projects of Uludag UniversityUludag University [2008/43]The present study was supported by a grant from The Commission of the Scientific Research Projects of Uludag University (2008/43). We are grateful to Soner Mamuk for the great technical assistance

The effects of LXR agonist GW3965 on vascular reactivity and inflammation in hypertensive rat aorta

WOS:000448413900034PubMed:30366037Aims: Liver X receptors (LXRs) play an important role in the regulation of cholesterol, fatty acid and glucose metabolisms together with inflammatory processes. In the present study, the effects of LXR agonist GW3965 on vascular reactivity and expression of functional proteins in DOCA-Salt induced hypertension were examined. Main methods: Hypertension was induced through unilateral nephrectomy and deoxycorticosterone-acetate (DOCA) injection (20 mg/kg, twice a week) for 6 weeks in male Wistar albino rats (8 weeks old). An LXR agonist GW3965 (10 mg/kg/day, i.p.) was administered to animals for last seven days. Key findings: GW3965 treatment reduced systolic blood pressures in hypertensive rats. Acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent vasorelaxations were decreased in hypertensive rats but not affected by GW3965. GW3965 treatment enhanced plasma nitrite levels in normotensive rats. KCl and phenylephrine (Phe)-induced vasocontractions were reduced in hypertensive groups and increased with GW3965 treatment. Decreased sarco/endoplasmic reticulum Ca2+- ATPase2 (SERCA2) expression in the hypertensive aorta was not changed by GW3965 treatment. Expression of inositoltrisphosphate receptor1 (IP3R1) was increased by GW3965 in normotensive animals. The nuclear factor kappaB (NF-kappa B) and tumor necrosis factor alpha (TNF-alpha) expressions were increased in hypertensive rats and reduced by GW3965 treatment. Significance: The results of study indicate that the LXR agonist, GW3965, exhibited a beneficial effect on increased blood pressure and improved hypertension-induced impairment in contractile activity of vessel and inflammatory markers in vascular tissue. Therefore, these effects of LXR agonists on vessel should be taken into account in experimental or therapeutic approaches to hypertension.TUBITAK-3001 projectTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114S170]; Ankara University Research FoundationAnkara University [16B0230004]This study was supported by research grants, from TUBITAK-3001 project (114S170) and Ankara University Research Foundation (16B0230004)

Age- and sex-dependent alteration of functions and epigenetic modifications of vessel and endothelium related biomarkers.

Aging is a main risk factor for development of cardiovascular diseases associated with the impairment of endothelial function in both sexes. In the present study, age-related changes in vascular responsiveness, epigenetic modifications of vessel wall, and blood biomarkers related to endothelial functions were examined in an age- and sex-dependent manner. Acetylcholine (ACh)-induced relaxations of the aorta were decreased in 3-, 6-, and 12-month-old rats compared to those in 1-month-old female rats. In males, maximum relaxations related to ACh were higher in 1- and 6-month-old rats than in 3- and 12-month-old rats. Plasma levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA) decreased with age in female rats, and total antioxidant capacity (TAC) and hydrogen sulfide (H 2S) levels displayed biphasic alterations. In male rats, plasma levels of NO, TAC, and ADMA decreased with age, and H2S levels increased. Aging also caused a sex-dependent alteration in epigenetic modification of vessels. Expressions of H3K27me2, H3K27me3, H3K36me2, and H3K36me3 were much higher in vessels of 12-month-old female rats compared to those in younger age groups. These results indicate that vascular functions, epigenetic modifications of vessels, and plasma levels of endothelium-related biomarkers are affected by age and sex. These findings could be important for the assessment of vascular status over the course of the life span

Inhibition of endoplasmic reticulum stress protected DOCA-salt hypertension-induced vascular dysfunction

WOS:000462806800005PubMed:30458302Hypertension has complex vascular pathogenesis and therefore the molecular etiology remains poorly elucidated. Endoplasmic reticulum stress (ERS), which is a condition of the unfolded/misfolded protein accumulation in the endoplasmic reticulum, has been defined as a potential target for cardiovascular disease. In the present study, the effects of ERS inhibition on hypertension-induced alterations in the vessels were investigated. In male Wistar albino rats, hypertension was induced through unilateral nephrectomy, deoxycorticosteroneacetate (DOCA) injection (20 mg/kg, twice a week) and 1% NaCl with 0.2% KCI added to drinking water for 12 weeks. An ERS inhibitor, tauroursodeoxycolic acid (TUDCA) (150 mg/kg/day, i.p.), was administered for the final four weeks. ERS inhibition in DOCA-salt induced hypertension was observed to have reduced systolic blood pressure, improved endothelial dysfunction, enhanced plasma nitric oxide (NO) level, reduced protein expressions of phosphorylated-double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (pPERK), 78 kDa glucose-regulated protein (GRP78), Inositol trisphosphate receptor1 (IP(3)R1) and Epidermal growth factor receptor (EGFR), increased expressions of endoplasmic reticulum Ca2+-ATPase2 (SERCA2) and B cell lymphoma2 (Bcl2) in vessels. These findings suggest that the beneficial effects of ERS inhibition on hypertension may be related to protection of vessel functions through restoration of endoplasmic reticulum calcium homeostasis, and apoptotic and mitotic pathways.Ankara University Research FoundationAnkara University [16B0230004]This study was supported by a research grant (16B0230004) from the Ankara University Research Foundation. The authors are grateful to Prof. Dr. H. Gurdal and B. Dalkilic for assisting with the Western Blot analysis

Diurnal Temporal Blood H2S Variations Correlate with the Circadian Rhythm of Vascular Contraction and Blood Pressure

Background: It is well known that blood pressure has a circadian rhythm in rat. However, the underlying mechanisms that modulate circadian rhythm of blood pressure have not been fully clarified. The aim of this study was to investigate the probable mechanisms that regulate time dependent variation of blood pressure. In present study, the correlations among the following s:alpha-1 adrenoceptor stimulated aortic contractions, thoracic aortic expression of Rho-kinase ll and myosin phosphatase target subunit-1 and blood biomarkers (nitric oxide, hydrogen sulfide {[}H2S] and total antioxidant capacity) that regulate blood pressure at six different times of the day and night were examined. Materials and Methods: Systolic blood pressure was measured every 4 h during a 24 h period in male albino Wistar rats by tail-cuff plethysmography. At each time point, contraction and relaxation responses of isolated thoracic aortas were recorded. The expression of protein from aortas was determined by western blot method. Nitric oxide, total antioxidant capacity and H2S levels were measured spectrophotometrically in plasma samples. One-way analysis of variance and student t-test was used to determine statistical differences. Results: Rat systolic blood pressure displayed a circadian rhythm, which reached the maximum at 05:00 am and minimum at 09;00 am. Diurnal variation of phenylephrine-induced contractions in the isolated thoracic aorta was also observed. Although, the Rho-kinase inhibitor Y-27632 reduced phenylephrine-induced contractions, the circadian pattern of the contractions did not change. Interestingly, Rho-kinase II and myosin phosphatase target subunit -1 protein expression in the thoracic aorta did not show significant changes throughout the day. Further, plasma levels of nitric oxide and total antioxidant capacity did not vary during the day. However, H2S levels in the systemic circulation showed circadian variation, which was the maximum at 01:00 am and minimum at 05;00 am. Conclusions: These results suggest that, in addition to alpha-1 adrenoceptor sensitivity of vessels, the circadian rhythm of plasma H2S could contribute to diurnal blood pressure variations. This highlights a potential novel experimental and therapeutic approach to blood pressure regulation

Age- and sex-dependent alteration of functions and epigenetic modifications of vessel and endothelium related biomarkers

Aging is a main risk factor for development of cardiovascular diseases associated with the impairment of endothelial function in both sexes. In the present study, age-related changes in vascular responsiveness, epigenetic modifications of vessel wall, and blood biomarkers related to endothelial functions were examined in an age- and sex-dependent manner. Acetylcholine (ACh)-induced relaxations of the aorta were decreased in 3-, 6-, and 12-month-old rats compared to those in 1-month-old female rats. In males, maximum relaxations related to ACh were higher in 1- and 6-month-old rats than in 3- and 12-month-old rats. Plasma levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA) decreased with age in female rats, and total antioxidant capacity (TAG) and hydrogen sulfide (H2S) levels displayed biphasic alterations. In male rats, plasma levels of NO, TAG, and ADMA decreased with age, and H2S levels increased. Aging also caused a sex-dependent alteration in epigenetic modification of vessels. Expressions of H3K27me2, H3K27me3, H3K36me2, and H3K36me3 were much higher in vessels of 12-month-old female rats compared to those in younger age groups. These results indicate that vascular functions, epigenetic modifications of vessels, and plasma levels of endothelium-related biomarkers are affected by age and sex. These findings could be important for the assessment of vascular status over the course of the life span

Effects of Ozone Treatment in Endotoxin Induced Shock Model in Rats

Objective: This study was focused on effects of ozone application on vital and biochemical parameters in rat model of endotoxin-induced shock. Materials and Methods: Lipopolysaccharide (LPS; 10 mg kg(-1), i.p.) induced shock model was used in male Wistar albino rats. Three different doses of ozone were used for this study (0.1, 0.3 and 1.0 mg kg(-1), i.p.). Tail-cuff method was preferred for measurements of systolic blood pressure and heart rate. Plasma nitric oxide (NO), total antioxidant capacity (TAC), asymmetric dimethylarginine (ADMA), aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) levels were detected as biochemical parameters. Results: Decline in systolic blood pressure and increment in heart rate of rats were observed an hour after injection of LPS. Ozone application did not possess any significant improvement on impaired systolic blood pressure and heart rate. Increased plasma levels of NO and decreased TAC levels with endotoxemic shock were reversed by ozone treatment. No significant effect on augmentated plasma levels of ALT by endotoxemia was observed with ozone application. On the other hand ADMA, AST and LDH levels were not changed with endotoxemia or ozone application. Conclusion: These results suggested that ozone treatment reversed the LPS-induced changes inplasma NO and TAC levels, but not other vital and biochemical parameters in rat model of endotoxin induced shock