Luteolin improves vasoconstriction function and survival of septic mice via AMPK/NF-κB pathway.

Septic shock, the leading cause of death in sepsis, is related to vasoconstriction dysfunction. To investigate the effects of Luteolin (LTL), a flavonoid polyphenol compound, on vasoconstriction dysfunction in septic mice and the underlying mechanism, cecal ligation and puncture (CLP) surgery was performed on wild-type C57BL/6 mice to induce septic shock. Mice were intraperitoneally injected with 0.2 mg/kg LTL within 10 min after CLP surgery with or without 20 mg/kg Compound C (AMPK inhibitor) (CC) 1 h before CLP surgery, and re-administrated every 12 h. The survival rate, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) were explored. After the mice were sacrificed, the vasoconstriction function, inflammatory indicators, and possible regulatory signaling pathways were examined. Our data showed that CLP decreased the survival rate, SAP, DAP, MAP, vasoconstriction function, and expression of ADRA1A and p-AMPK/AMPK, as well as increased the mRNA expression of inflammatory cytokines and iNOS, the serum levels of inflammatory cytokines, and the levels of iNOS, p-p65/p65, and p-IκBα/IκBα in aortas (P < 0.05), which could be reversed by LTL treatment (P < 0.05). However, inhibition of AMPK could abolish the protective effects of LTL (P < 0.05). In conclusion, our study manifested that LTL could prevent vasoconstriction dysfunction and increase survival of septic mice via activating AMPK, which suggested that LTL could be a novel therapeutic option for patients with sepsis.

2-Benzyllawsone protects against polymicrobial sepsis and vascular hyporeactivity in swiss albino mice.

BACKGROUND: Novel naphthoquinone, 2-benzyllawsone (LT-9) was evaluated against vascular hyporeactivity and sepsis in cecal ligation and puncture (CLP) model in mice in view of its preliminary antibacterial and anti-inflammatory properties and to explore whether pretreatment with the molecule could restore vascular tone and contractile response to norepinephrine. METHODS: Evaluation of LT-9 against vascular hyporeactivity, hypotension, and sepsis-related inflammation and infection was carried out in the CLP model in Swiss albino mice and aortic smooth muscle cells in vitro. RESULTS: LT-9 showed potent reversal of the vascular hyporeactivity in CLP mice aorta. The increased contraction response to norepinephrine in CLP mouse aorta by LT-9 was mediated by opening of L-type voltage-dependent calcium channels (VDCC) verified by ex vivo experiment where LT-9 enhanced contraction response to CaCl2 in the aorta while abolishing the contraction response of known VDCC opener Bay K8644. LT-9 in aortic smooth muscle cells showed Fluo-4 mediated increase in calcium fluorescence. Oral administration of LT-9 at 50 and 100 mg kg-1 day-1 for 15 days significantly enhanced the mean survival time, improved hemodynamic and Electrocardiogram (ECG) profile, and aortic tissue reactivity in CLP mice. Further, LT-9 significantly reversed the perturbation of the expression profile of inflammatory cytokines, reduced the splenic microbial load, and was well tolerated in oral toxicity. CONCLUSIONS: LT-9 showed potent biological activity against sepsis and was found to be well tolerated in the toxicity study in Swiss albino mice and showed promise for the benzyllawsone class of molecules against sepsis for the development of novel pharmacophore.

Inhibition of the norepinephrine transporter rescues vascular hyporeactivity to catecholamine in obstructive jaundice.

In patients with obstructive jaundice, the cardiovascular system exhibits hypotension and vascular hyporeactivity. Most norepinephrine is taken up through the neuronal norepinephrine transporter (NET), which is implicated in cardiovascular diseases. A previous study demonstrated that pharmacological NET inhibition could increase resting blood pressure. However, the role of NETs in vascular hyporeactivity induced by obstructive jaundice is poorly understood. This study used the NET inhibitor nisoxetine and a rat model of bile duct ligation (BDL) to investigate whether NET is associated with BDL-induced vascular hyporeactivity. Rats were injected with nisoxetine via the tail vein for 7 consecutive days after BDL. Samples of the superior cervical sympathetic ganglion (SCG) and thoracic aortic rings were processed for investigations. Our results showed that NET expression in the SCG was significantly increased after BDL. Nisoxetine prevented the augmentation of NET expression, increased α1-adrenoceptor activation, and enhanced the weakened contractile responses of thoracic aortic rings after BDL. Our study demonstrates that nisoxetine plays a protective role in BDL-induced vascular hyporeactivity through increased α1-adrenoceptor activation in rats.

Tubeimoside I improves survival of mice in sepsis by inhibiting inducible nitric oxide synthase expression.

Sepsis is a disease with high mortality rate worldwide and inducible nitric oxide (iNOS) induced vascular hyporeactivity plays a key role in it. There is no effective drug to treat vascular hyporeactivity specifically. Tubeimoside I (TBM) is a triterpenoid saponin isolated from Rhizoma Bolbostemmatis. In this study, we found that 4 mg/kg TBM intraperitoneally injected 1 h before cecal ligation and puncture (CLP) partially improved survival, ameliorated mean arterial pressure (MAP) and enhanced vascular responsiveness to norepinephrine (NE) and KCl in wild-type septic mice. CLP activated TLR4-MyD88-NF-κB-iNOS pathway was also inhibited by TBM both in vitro and in vivo. However, iNOS gene knockout counteracted the protection provided by TBM. We conclude that TBM protects mice in sepsis by reducing excessive NO production through inhibiting the TLR4-MyD88-NF-κB-iNOS pathway. Our study suggests a possible therapeutic application of TBM in sepsis.

Betulinic acid attenuates lipopolysaccharide-induced vascular hyporeactivity in the rat aorta by modulating Nrf2 antioxidative function.

Betulinic acid (BA), a pentacyclic triterpenoid, has been reported to inhibit cardiovascular dysfunction under sepsis-induced oxidative stress. Nuclear factor erythroid-2 related factor-2 (Nrf2) is regarded as a key transcription factor regulating expression of endogenous antioxidative genes. To explore the preventive effects of BA against vascular hyporeactivity and the related antioxidative mechanism in sepsis, contraction and relaxation in aortas isolated from lipopolysaccharide (LPS)-challenged rats were performed. Male Sprague-Dawley rats were pretreated with brusatol (Bru, 0.4 mg/kg/2 days, i.p.), an inhibitor of Nrf2, and BA (10, 25, 50 mg/kg/day, i.g.) for 3 days and injected with LPS (10 mg/kg, i.p.) at the 4th day. Rats were anesthetized and killed by cervical dislocation after they were treated with LPS for 4 h. Thoracic aortas were immediately dissected out to determine contraction and relaxation using the organ bath system. Pro-inflammatory factors interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and oxidative stress were measured in aortic tissues and plasma. mRNA expression of Nrf2-regulated antioxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), in rat aortas was determined. Increases of IL-1ß, TNF-α, nitric oxide, and malondialdehyde and the decrease of glutathione induced by LPS were significantly attenuated by pretreatment with different doses of BA in plasma and aortas (p < 0.05 versus LPS), all of which were blocked by Bru (p < 0.01). Inhibition of phenylephrine (PE)- and KCl-induced contractions and acetylcholine (ACh)-induced vasodilatation in aortas from LPS-challenged rats was dose-dependently reduced by BA (p < 0.05; percentage improvements by BA in PE-induced contraction were 55.38%, 96.41%, and 104.33%; those in KCl-induced contraction were 15.11%, 23.96%, and 22.96%; and those in ACh-induced vasodilatation were 16.08%, 42.99%, and 47.97%), all of which were reversed by Bru (p < 0.01). Improvements of SOD, GPx, and HO-1 mRNA expression conferred by BA in LPS-challenged rat aortas were inhibited by Bru (p < 0.01; 145.45% versus 17.42%, 160.69% versus 22.76%, and 166.88% versus 23.57%). These findings suggest that BA attenuates impairments of aortic contraction and relaxation in LPS-challenged rats by activating Nrf2-regulated antioxidative pathways.

Dihydromyricetin improves vascular hyporesponsiveness in experimental sepsis via attenuating the over-excited MaxiK and KATP channels.

CONTEXT: Dihydromyricetin (DMY) has oxidation resistance, anti-inflammatory and free radical scavenging capabilities. The preventive effects of DMY for vascular hyporeactivity remain unclear. OBJECTIVE: This study investigates the preventive effects of DMY in vascular hyporeactivity. MATERIALS AND METHODS: The experimental sepsis was induced by transvenous administration of lipopolysaccharide (LPS) to Sprague-Dawley (SD) rats. DMY-treated rats received daily administration of DMY, 5 µg/kg dissolved in DMSO through the tail vein for 7 days. The invasive mean arterial pressure (MAP) of the caudal ventral artery was measured. Dose-response curves for norepinephrine (NE, doses from 10-9 to 10-6 M) were obtained in isolated thoracic aorta in a cumulative manner. The function of MaxiK and KATP channels were investigated using whole-cell patch clamp recording. The Elisa was adopted to measure the serum concentration of NO, MDA, 3-NT, IL-1ß and TNF-α. RESULTS: The increased MAP in septic rats induced by vasopressor agents was smaller than that in control rats. However, the % of increased MAP induced by vasopressor agents was raised by DMY injection (NE: 20.4 ± 8.495 vs. 15.16 ± 5.195%; AVP: 14.05 ± 2.459 vs. 9.583 ± 2.982%, p < 0.05). The vascular hyporesponsiveness to NE (10-6 M) in vitro. was increased by 51% in LPS + DMY group compared with that in LPS + Con group (2.74 ± 0.81 vs. 1.82 ± 0.92 g, p < 0.05). Charybdotoxin (a potent MaxiK channel blocker) and glibenclamide (a KATP channel blocker) pretreatment, instead of 4-aminopyridine (4-AP) and BaCl2, could diminish the DMY-induced improvement of vasoconstrictor hyporeactivity (ChTX: 73.2 ± 11.8 vs. 71.8 ± 13.5%; Glib: 63.1 ± 12.5 vs. 58.1 ± 13.7%, p > 0.05). DMY blunted the highly sensitized MaxiK and KATP channels of arterial smooth muscle cells isolated from the thoracic aorta of LPS rats. DMY decreased the serum level of NO, MDA, IL-1ß and TNF-α, which had increased in LPS rats. DISCUSSION AND CONCLUSIONS: Our results indicate that DMY administration ameliorated the impaired contractility of the rat aorta in experimental sepsis. Such an effect is mediated by normalization of the over-excited MaxiK and KATP, channels possibly via oxidative stress inhibition.

Effects of SPAK on vascular reactivity and nitric oxide production in endotoxemic mice.

Vasoplegia impedes therapeutic interventions to restore vascular tone, leading to severe hypotension, poor tissue perfusion, and multiple organ failure in septic shock. High levels of circulating nitric oxide (NO) play a crucial role in endotoxin-induced vascular hyporeactivity. Proinflammatory cytokines have been implicated in the induction of inducible NO synthase and overproduction of NO. Anti-inflammatory therapy can diminish NO formation and improve vascular hyporeactivity in septic shock. STE20/SPS1-realted proline/alanine-rich kinase (SPAK) has been reported to activate mitogen-activated protein kinase and contribute to intestinal inflammation. Thus, we evaluated the roles of SPAK in NO production and vascular hyporeactivity in endotoxemic animals. Male wild-type and SPAK deficiency mice were intraperitoneally administered vehicle or Escherichia coli lipopolysaccharide (LPS, 50mg/kg). The changes of systolic blood pressure and plasma nitrate and nitrite levels were measured during the experimental period. Thoracic aortas were exercised to assess vascular reactivity and SPAK expression. In the present study, mice in endotoxin model showed severe hypotension and hyporeactivity to serotonin, phenylephrine (PE), and acetylcholine in the aortic rings. Phosphorylated SPAK expression in the aorta and NO levels in the plasma were also increased in animals with endotoxic shock. However, deletion of SPAK not only reduced the elevation of NO levels but also improved vascular hyporeactivity to serotonin and PE in endotoxemic mice. Taken together, SPAK could be involved in the NO overproduction and vascular hyporesponsiveness to vasoconstrictors in endotoxic shock. Thus, inhibition of SPAK could be useful in the prevention of endotoxin-induced vascular hyporeactivity.

Myoendothelial gap junctions mediate regulation of angiopoietin-2-induced vascular hyporeactivity after hypoxia through connexin 43-gated cAMP transfer.

Angiopoietin-2 (Ang-2) contributes to vascular hyporeactivity after hemorrhagic shock and hypoxia through upregulation of inducible nitric oxide synthase (iNOS) in a vascular endothelial cell (VEC)-specific and Ang-2/Tie2 receptor-dependent manner. While iNOS is primarily expressed in vascular smooth muscle cells (VSMCs), the mechanisms of signal transfer from VECs to VSMCs are unknown. A double-sided coculture model with VECs and VSMCs from Sprague-Dawley rats was used to investigate the role of myoendothelial gap junctions (MEGJs), the connexin (Cx) isoforms involved, and other relevant mechanisms. After hypoxia, VSMCs treated with exogenous Ang-2 showed increased iNOS expression and hyporeactivity, as well as MEGJ formation and communication. These Ang-2 effects were suppressed by the MEGJ inhibitor 18α-glycyrrhetic acid (18-GA), Tie2 siRNA, or Cx43 siRNA. Reagents antagonizing cAMP or protein kinase A (PKA) in VECs inhibited Cx43 expression in MEGJs, decreasing MEGJ formation and associated communication, after hypoxia following Ang-2 treatment. The increased cAMP levels in VSMCs and transfer of Alexa Fluor 488-labeled cAMP from VECs to VSMCs, after hypoxia following Ang-2 treatment, was antagonized by Cx43 siRNA. A cAMP antagonist added to VECs or VSMCs inhibited both increased iNOS expression and hyporeactivity in VSMCs subjected to hypoxia following Ang-2 treatment. Based on these findings, we propose that Cx43 was the Cx isoform involved in MEGJ-mediated VEC-dependent regulation of Ang-2, which induces iNOS protein expression and vascular hyporeactivity after hypoxia. Cx43 was upregulated by cAMP and PKA, permitting cAMP transfer between cells.

Coenzyme Q10 improves the survival, mesenteric perfusion, organs and vessel functions in septic rats.

BACKGROUND: Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier in the mitochondrial respiratory chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to investigate the effects of CoQ10 on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. METHODS: Wistar rats were divided into Sham, CLP, Sham+CoQ10, CLP+CoQ10 subgroups. CoQ10 (10mg/kg/day) or vehicle (olive oil; 1mL/kg/day) was intraperitoneally injected for 15days. At 16th day, Sham or CLP operation was performed. 20h after the operations, MABF and phenylephrine responses of isolated aortic rings were measured. Tissue samples were obtained for histopathological and biochemical evaluations. Furthermore, survival rates were monitored throughout 96h. RESULTS: CoQ10 prevented mesenteric hypoperfusion and aortic dysfunction induced by CLP. Survival rate was %0 at 46th h in CLP group, but in CLP+CoQ10 group it was 37.5% at the end of 96h. CLP-induced elevations of serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were blocked by CoQ10. CoQ10 restored the increased liver, lung, spleen and kidney malondialdehyde levels and as well as reduced liver and spleen glutathione levels. The protective effects of CoQ10 on multiple organ damage were also observed histopathologically. CONCLUSIONS: CoQ10 showed protective effects in sepsis due to its preservative effects on mesenteric perfusion, aortic function and also its anti-inflammatory and antioxidative effects.

Thymoquinone protects against the sepsis induced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ damage in rats.

BACKGROUND: Thymoquinone (TQ) is a potent cytoprotective, antioxidant and anti-inflammatory agent. We aimed to investigate the possible protective effects of TQ on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in a murine sepsis model induced by cecal ligation and puncture (CLP). METHODS: Wistar rats were divided into the following four groups: Sham, CLP, Sham+TQ and CLP+TQ. TQ (1mg/kg/day) or vehicle (dimethyl sulfoxide, 1mL/kg/day) was intraperitoneally injected for 3 days. At 4th day Sham or CLP operation was applied. 20h after the operations, MABF and contractile responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for histopathological and biochemical examinations. Also, survival rates were recorded throughout 96h. RESULTS: TQ ameliorated mesenteric hypoperfusion and partially attenuated aortic dysfunction induced by CLP. Survival rate was %0 at 42nd h in CLP group, but in CLP+TQ group it was 33.4% at the end of 96h. Serum levels of AST, ALT, LDH, BUN, Cr and inflammatory cytokines (tumor necrosis factor-α, interleukin-1 ß and interleukin-6) increased in CLP group that were prevented by TQ. The decreases in liver, spleen and kidney glutathione levels and the increases in liver, lung, kidney and spleen malondialdehyde levels induced by CLP were inhibited by TQ. The histopathological protective effects of TQ on multiple organ damage due to CLP were also observed. CONCLUSION: TQ has ameliorative effects on sepsis due to its protective effects on mesenteric perfusion, contractile function of aorta and its anti-inflammatory and antioxidative effects.

Celecoxib administration reduced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ injury in septic rats.

BACKGROUND: The cyclooxygenase (COX)-2 overexpression is associated with vascular injury and multiple organ failure in sepsis. However, constitutive COX-1 and basal COX-2 expressions have physiological effects. We aimed to investigate the effects of partial and selective COX-2 inhibition without affecting constitutive COX-1 and basal COX-2 activities by celecoxib on mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries, and survival in septic rats accomplished by cecal ligation and puncture (CLP). METHODS: Wistar rats were allocated into Sham, CLP, Sham+celecoxib, CLP+celecoxib subgroups. 2h after Sham and CLP operations, celecoxib (0.5mg/kg) or vehicle (saline; 1mL/kg) was administered orally to rats. 18h after drug administrations, MABF and responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for biochemical and histopathological examinations. Furthermore, survival rate was monitored throughout 96h. RESULTS: Celecoxib ameliorated mesenteric hypoperfusion and partially improved aortic dysfunction induced by CLP. Survival rate was%0 at 49th h in CLP group, but in CLP+celecoxib group it was 42.8% at the end of 96h. Serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were increased in CLP group that were prevented by celecoxib. The decreases in liver and spleen glutathione levels and the increases in liver, lung, spleen and kidney malondialdehyde levels in CLP group were blocked by celecoxib. The histopathological protective effects of celecoxib on organ injury due to CLP were also observed. CONCLUSIONS: Celecoxib has protective effects on sepsis due to its preservative effects on mesenteric perfusion, aortic function and its anti-inflammatory and antioxidative effects.

Beneficial effect of cyclosporine A on traumatic hemorrhagic shock.

BACKGROUND: Vascular hyporeactivity plays an important role in severe trauma and shock. We investigated the beneficial effect of cyclosporine A (CsA) on traumatic shock and its relationship to vascular reactivity improvement and mitochondrial permeability transition pore (MPTP). MATERIALS AND METHODS: Sodium pentobarbital-anesthetized rats were used to induce traumatic hemorrhagic shock by left femur fracture and hemorrhage, the beneficial effects of CsA (1, 5, and 10 mg/kg, intravenously) on animal survival, cardiovascular function, tissue blood perfusion, and mitochondrial function of vital organs were observed. In addition, hypoxia-treated vascular smooth muscle cells from normal rats were used to investigate the relationship of this beneficial effect of CsA to Rho-associated serine/threonine kinase (ROCK) and protein kinase C. RESULTS: CsA prolonged the survival time and increased the 24-h survival rate of traumatic hemorrhagic shock (31%, 56%, and 56% in 1, 5, and 10 mg/kg CsA group versus 25% in lactated Ringer solution group). Five milligrams per kilogram of CsA had the best effect, which stabilized and improved the hemodynamics, increased the tissue blood flow, and improved the liver and kidney function including its mitochondrial function in shock rats. CsA had no significant influences on the production of inflammatory mediators and cardiac output after traumatic hemorrhagic shock. Further results indicated that CsA significantly improved the vascular constriction and dilation reactivity of superior mesenteric artery to norepinephrine and acetylcholine, which was antagonized by ROCK inhibitor, Y27632, but not by protein kinase C inhibitor, staurosporine. Further studies showed that CsA restored hypoxia-induced decrease of ROCK activity and inhibited the opening of MPTP in hypoxia-treated vascular smooth muscle cells. CONCLUSIONS: CsA is beneficial for the treatment of traumatic hemorrhagic shock. The mechanism is mainly through improving the vascular reactivity, stabilizing the hemodynamics, and increasing tissue perfusion. This beneficial effect of CsA is related to the inhibitory effect of CsA on MPTP opening. ROCK is an important regulator molecule in this process.

Beneficial and side effects of arginine vasopressin and terlipressin for septic shock.

Arginine vasopressin (AVP) and its analog, terlipressin (TP), were all demonstrated beneficial for septic shock. What advantages and disadvantages that AVP and TP have for septic shock as well as the mechanism, however, are not completely known. With cecal ligation and puncture-induced septic shock rats and lipopolysaccharide-induced septic shock rabbits, we systematically compared the beneficial and side effects of AVP and TP, in septic shock and the sex difference, and investigated their relationship to Rho kinase and calcium sensitivity. The results indicated that low dose of TP (2.6 µg/kg/h) in combination with norepinephrine (NE) improving vascular reactivity and animal survival were superior to a small dose of AVP (0.03 U/kg/h) in septic shock rats and rabbits. This improving effect of AVP and TP on vascular reactivity was closely related to the activation of Rho-kinase and Rho-kinase-mediating vascular calcium sensitization. A small dose of TP did not result in hyponatremia, did not increase blood bilirubin and decrease platelet count, whereas AVP did. Animal survival and vascular reactivity in female rats after TP or AVP administration were slightly better than male rats, while there were no significant differences. It was suggested that a small dose of TP has better beneficial effect and less side effects on septic shock than AVP. AVP and TP improving vascular reactivity is closely related to Rho-kinase activation and calcium sensitivity improvement. TP or plus NE may be more appropriate for early emergency care for severe septic shock than AVP.

Dexamethasone effects on vascular flow and organ injury in septic mice.

BACKGROUND: To demonstrate the effects of low-dose dexamethasone treatment on mesenteric artery blood flow, oxidative injury, vascular reactivity, and survival in Swiss albino mice with intra-abdominal polymicrobial sepsis accomplished by cecal ligation and puncture (CLP). METHODS: Mice were allocated to CLP + saline, CLP + dexamethasone, sham + saline, and sham + dexamethasone subgroups to evaluate blood flow, organ injury, and vascular response to consecutive phenylephrine administrations at 24, 48, and 72 h. Survival rates were also evaluated in a different group of mice. Dexamethasone (1 mg/kg/d) and saline (4 mL/kg/d) were administered intraperitoneally to mice 2 h after CLP or sham procedure, whichever appropriate, and repeated once a day until evaluation time at 48 and 72 h. Relaparotomy was performed at the concerned time and mesenteric blood flow was measured, and liver, lung, and peritoneum samples were obtained. Alteration in mesenteric blood flow response to intravenous phenylephrine injections was recorded at the related time intervals in different mice groups. Survival group was followed up by 7-d administration of dexamethasone or saline for 18 d. RESULTS: The significant fall in mesenteric blood flow after CLP ameliorated with dexamethasone treatment at 48 and 72 h. Dexamethasone also diminished the malonyl dialdehyde level, which is an indicator of organ injury raised after CLP, at 24 h in liver, lung, and peritoneum samples. Dexamethasone therapy has significantly enhanced the vascular response to phenylephrine injections at all doses; however, no change was observed in survival rates. CONCLUSIONS: Low-dose dexamethasone has beneficial effects on mesenteric blood flow and organ injury in experimental sepsis models.