Preparation of sheet-like covalent organic frameworks and their application for efficient preconcentration of 4-(tert-octyl)-phenol and 4-nonylphenol in textiles.

In the design of highly ordered (covalent organic frameworks) COFs with "ordered domains size and orientation" construction in a well-defined arrangement, the molecular monomers are the key factors. Here, the effect of molecular monomers on the construction of COFs has been studied, and two kinds of molecular monomers, i.e., ethanediamine (flexible amine ligand) and 4,4'-diaminobiphenyl (rigid amine ligand) have been used for developing sheet-like COFs-I and sheet-like COFs-II, respectively. Furthermore, they have been evaluated in the dispersive solid phase extraction (dSPE) procedure for textiles prior to the analysis of alkylphenol by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). The results showed that, the optimal usage amount of sheet-like COFs-II used in the dSPE procedure was less than that of sheet-like COFs-I, which may be explained by much higher adsorption capacity of sheet-like COFs via hydrogen-bonding and π-π stacking interactions. Rectilinear calibration graphs were obtained for 4-(tert-octyl)-phenol (4-tOP) and 4-nonylphenol (4-NP) in the range 0.2-20 µg/kg with determination coefficient (r2) higher than 0.9990, and the limits of detection (LODs) of 4-tOP and 4-NP were 0.039 µg/kg and 0.048 µg/kg, respectively. The developed method has been successfully applied to analysis of 50 textile samples, in which 4-tOP and 4-NP were found in six samples with concentrations in the range of 1.6 µg/kg-20.9 µg/kg.

HDAC-selective Inhibitor Cay10603 Has Single Anti-tumour Effect in Burkitt's Lymphoma Cells by Impeding the Cell Cycle.

Histone deacetylases (HDACs) inhibitors are novel in cancer therapy nowadays. HDAC6-selective inhibitors exert advantageous effects due to higher selectivity and less toxicity. We explored the anti-tumor effect and the molecular mechanism of cay10603, a potent HDAC6 inhibitor in Burkitt's lymphoma cells. Our study revealed cay10603 inhibited the proliferation of Burkitt's lymphoma cell lines, and induced caspase-dependent apoptosis. Cay10603 inhibited the expression of CDKs and cyclins to impede cell cycle progression in both Burkitt's lymphoma cell lines. Cay10603 also showed the additive effect with vp16 notably. Our data presented the promising anti-tumor effect of cay10603 in the Burkitt's lymphoma therapy.

Dexmedetomidine Protects Against Multi-Organ Dysfunction Induced by Heatstroke via Sustaining The Intestinal Integrity.

Previous studies have indicated that gut-derived endotoxin played a pivotal role for aggravating systemic inflammatory response to multi-organ dysfunction under heatstroke. Dexmedetomidine (DEX) could protect against inflammation and multi-organ injury in various scenarios. The aim of this study was to explore the protective effect of DEX on heatstroke and the mechanism involved. Male C57BL/6 mice were placed in a controlled climate chamber (40 ±â€Š1°C) until the maximum core temperature (Tc, Max) of 42.7°C, the received criterion of heatstroke, was attained, DEX (25 µg/kg) or 0.9% saline was injected intraperitoneally immediately. The results showed that DEX could significantly attenuate multi-organ injury induced by heatstroke, simultaneously decrease levels of serum inflammatory cytokines through inhibiting the intestinal nuclear factor-κB activation. Furthermore, to assess the effects of DEX on intestine mucosal barrier under heatstroke, the levels of plasma endotoxin, FD4, and D-lactate were detected and the expression of tight junction proteins occludin and ZO-1 was analyzed by western blot and immunohistochemistry. Meanwhile, transmission electron microscopy was employed to confirm the ultrastructure of intestine. Interestingly, we found that DEX decreased the intestinal permeability and sustained the integrity of intestinal barrier. Finally, to evaluate the anti-apoptosis effect of DEX, the pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2 were analyzed by western blot, and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) staining was conducted. The results showed that DEX decreased TUNEL-positive cells induced by heatstroke in a Bax/Bcl-2-related manner. Taken together, our results indicate that DEX could protect against inflammation and multi-organ injury induced by heatstroke via sustaining the intestinal integrity.

Two unusual 3D honeycomb networks based on Wells-Dawson arsenomolybdates with d10 transition-metal-pyrazole connectors.

Herein, two Wells -Dawson-type arsenomolybdates, formulated as [Cu(pyr)2]6[As2Mo18O62] (1) and [Ag(pyr)2]6[As2Mo18O62] (2) (pyr = pyrazole), were hydrothermally synthesized and structurally characterized via single-crystal X-ray diffraction, elemental analysis, IR and UV-vis-NIR spectroscopies, XPS, XRD, and TG analysis. The structural analysis indicated that compounds 1 and 2 were isomorphic. They are the first reported 3D honeycomb structures of Wells-Dawson-type arsenomolybdates. The [M(pyr)2] (M = Cu and Ag) connected with [As2Mo18O62]6- polyoxoanions to form the {812·123}{8}3 topological structure. The contributions of organic ligands, pH value, reaction temperature, and transition-metal (TM) to the construction of 3D networks were elucidated. Furthermore, compounds 1 and 2 exhibited fluorescence properties in the solid state at room temperature, highly efficient catalytic ability for the degradation of five organic dyes (MB, RhB, MO, AP, and CR) under UV irradiation, and obvious electrocatalytic activities for the reduction of H2O2. The mechanisms of photocatalysis and electrocatalysis have also been discussed in detail.

NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages.

A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death. We observed an increasing proportion of pyroptosis and elevating Caspase-1 activation in 10 and 20 Gy radiation groups. Nlrp3 knock out significantly diminished the quantity of cleaved-Caspase-1 (p10) and IL-1ß as well as the proportion of pyroptosis. Additionally, in vivo research shows that 9.5 Gy of radiation promotes Caspase-1 activation in marginal zone cells and induces death in mice, both of which can be significantly inhibited by knocking out Nlrp3. Thus, based on these findings, we conclude that the NLRP3 inflammasome activation mediates radiation-induced pyroptosis in BMDMs. Targeting NLRP3 inflammasome and pyroptosis may serve as effective strategies to diminish injury caused by radiation.

Activation of the NLRP3 inflammasome in lipopolysaccharide-induced mouse fatigue and its relevance to chronic fatigue syndrome.

BACKGROUND: The NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3) is an intracellular protein complex that plays an important role in innate immune sensing. Its activation leads to the maturation of caspase-1 and regulates the cleavage of interleukin (IL)-1ß and IL-18. Various studies have shown that activation of the immune system plays a pivotal role in the development of fatigue. However, the mechanisms underlying the association between immune activation and fatigue remained elusive, and few reports have described the involvement of NLRP3 inflammasome activation in fatigue. METHODS: We established a mouse fatigue model with lipopolysaccharide (LPS, 3 mg/kg) challenge combined with swim stress. Both behavioural and biochemical parameters were measured to illustrate the characteristics of this model. We also assessed NLRP3 inflammasome activation in the mouse diencephalon, which is the brain region that has been suggested to be responsible for fatigue sensation. To further identify the role of NLRP3 inflammasome activation in the pathogenesis of chronic fatigue syndrome (CFS), NLRP3 KO mice were also subjected to LPS treatment and swim stress, and the same parameters were evaluated. RESULTS: Mice challenged with LPS and subjected to the swim stress test showed decreased locomotor activity, decreased fall-off time in a rota-rod test and increased serum levels of IL-1ß and IL-6 compared with untreated mice. Serum levels of lactic acid and malondialdehyde (MDA) were not significantly altered in the treated mice. We demonstrated increased NLRP3 expression, IL-1ß production and caspase-1 activation in the diencephalons of the treated mice. In NLRP3 KO mice, we found remarkably increased locomotor activity with longer fall-off times and decreased serum IL-1ß levels compared with those of wild-type (WT) mice after LPS challenge and the swim stress test. IL-1ß levels in the diencephalon were also significantly decreased in the NLRP3 KO mice. By contrast, IL-6 levels were not significantly altered. CONCLUSIONS: These findings suggest that LPS-induced fatigue is an IL-1ß-dependent process and that the NLRP3/caspase-1 pathway is involved in the mechanisms of LPS-induced fatigue behaviours. NLRP3/caspase-1 inhibition may be a promising therapy for fatigue treatment.

Is the CARD8 rs2043211 polymorphism associated with susceptibility to Crohn's disease? A meta-analysis.

Many studies have reported the association between the CARD8 gene polymorphism rs2043211 and the susceptibility to Crohn's disease (CD), but the results have remained quite contradictory. Therefore, the aim of the meta-analysis was to explore whether the CARD8 rs2043211 polymorphism has an effect on CD risk. We performed a systematic literature search for related articles published up to July 2014 in multiple databases. Six eligible articles containing eight studies were selected. Odds ratios (ORs) as well as their corresponding 95% confidence intervals (CIs) were used to estimate the association between the CARD8 polymorphism and CD risk in different genotypic models. Heterogeneity analysis was also performed and publication bias was taken into account. Subgroup analyses were conducted according to different ethnicities, as well as different types of CD. In the pooled analyses, no statistical significant association was found between the CARD8 polymorphism and CD risk in the overall population or Caucasian subgroup in the additive model (overall population: OR = 0.93, 95% CI = 0.87-1.01; Caucasian: OR = 0.93, 95% CI = 0.83-1.05). However, subgroup analysis based on different CD types showed a significant association between the CARD8 polymorphism and CD risk in the additive model (ileal CD: OR = 0.83, 95% CI = 0.70-0.98; stenotic or fistulizing CD: OR = 0.81, 95% CI = 0.72-0.92). Our results indicated that CD may involve different types of pathogenesis and have variable clinical manifestations. In patients with ileal, stenotic or fistulizing CD, the mutant-type rs2043211 polymorphism may generate a potentially protective effect.

Association between vitamin D receptor gene polymorphisms and susceptibility to Parkinson's disease: a meta-analysis.

Previous studies have reported an association between vitamin D receptor (VDR) gene polymorphisms and Parkinson's disease (PD), but the results were controversial. To explore whether VDR gene polymorphisms have an effect on PD risk, we performed this meta-analysis to evaluate the association between three VDR gene polymorphisms (Bsml, Apal, Taql) and PD susceptibility. We performed a systematic literature search for articles published up to February 2014 in multiple databases and selected seven eligible studies. Four studies were included for each polymorphism. Odds ratios (ORs) as well as their corresponding 95% confidence intervals (CIs) were used to estimate the association between VDR gene polymorphisms and PD risk in four phenotype models. Subgroup analysis and publication bias were also performed. Heterogeneity analysis and sensitivity analysis were performed if necessary. We failed to detect any association between Apal, Bsml, Taql polymorphisms and PD susceptibility in all four genetic models. In subgroup analysis grouped by ethnicity, no significant association was detected. The present meta-analysis indicates that the VDR genetic polymorphisms Bsml, Apal and Taql are not associated with susceptibility to PD. Because of the limited number of included studies, the results should be cautiously interpreted. More carefully designed studies are needed to verify our results.

[Macrozoobenthos community structure and water quality evaluation of Tian'e Zhou Oxbows].

A quarterly investigation of the macrozoobenthos community in Tian'e Zhou Yangtze Oxbows was conducted during January 2011 to October 2011. And water quality was assessed based on the benthic macroinvertebrate community structure. It shows that, a total of 30 macrozoobenthos species were found, among which, Insecta (14 species) , Mollusca (6 species), Oligochaeta (8 species) and others (2 species) accounted for 46.67%, 20.00%, 26.67%, and 6.67% of the total, respectively. The dominant species were Clinotanypus, Cryptochironomus digitatus, Limnodrilus claparedeianus, and Limnodrilus hoffmeisteri. The average annual density and biomass of macrozoobenthos were 558.37 ind · m(-2), and 14.03 g · m(-2), respectively. The density of macrozoobenthos was highest in the winter and lowest in the spring, the biomass was highest in the autumn and lowest in the spring. In ten sampling points, No. 8 had the highest density, 1986.00 ind · m(-2), No. 7 had the highest biomass, 50.22 g · m(-2), and No. 6 had the lowest density and biomass, 98.00 ind · m(-2) and 0.85 g · m(-2). The evaluation with Shannon-Wiener diversity index (H'), Margalef richness index (d), Family-level biotic index (FBI), and integrated pollution index (BI) indicated that the overall water quality of the Tian'e Zhou Oxbow was moderate-heavy pollution (III-IV). As compared to that in 2003-2004 (II), the water quality of Tian'e Zhou Oxbow was somewhat decreased.

E-selectin deficiency attenuates brain ischemia in mice.

AIMS: To determine whether E-selectin deficiency can attenuate brain ischemia in a mouse model of focal cerebral ischemia. METHODS: E-selectin was determined in spontaneously hypertensive rats (SHRs) and stroke-prone spontaneously hypertensive rats (SHR-SPs). E-selectin knockout (Es(-/-) ) mice and wild-type control (WT) mice underwent permanent distal middle cerebral artery occlusion (MCAO). Behavioral analyses were performed followed by the measurement of infarct areas. Myeloperoxidase (MPO) protein was determined by Western blot. IL-6, IL-1ß, and TNF-α were detected by ELISA. In situ detection of apoptotic cells was performed by TUNEL staining. RESULTS: The brain and serum E-selectin levels were higher in SHR-SPs than in SHRs (P < 0.05) after salt intake. E-selectin deficiency improved neurological function and reduced infarct area in cerebral ischemic mice. MPO and IL-1ß were lower in Es(-/-) mice than in WT mice. In addition, the number of apoptotic cells in Es(-/-) mice was significantly less than in WT mice after MCAO. CONCLUSIONS: E-selectin deficiency presents protective effect on cerebral ischemia. This protective effect is likely achieved by the inhibition of inflammation and apoptosis.

Synergism of telmisartan and amlodipine on blood pressure reduction and cardiorenal protection in hypertensive rats.

AIM: This study was designed to investigate the effects of telmisartan and amlodipine on reduction of blood pressure (BP), myocardial hypertrophy, and renal injury in hypertensive rats. METHOD: In acute experiments, the BP was measured in conscious freely moving rats. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (1, 2, 4 mg/kg), telmisartan (4, 8, 12, 16, 20 mg/kg), and their different combinations (4 + 4, 2 + 4, 4 + 8, 4 + 12, 1 + 4, 2 + 8, 4 + 16, 2 + 12, 1 + 8, 2 + 16, 2 + 20, 1 + 12, 1 + 16, 1 + 20 mg/kg). The probability sum test (q test) was used to evaluate the synergistic action on BP reduction. In two-kidney, one-clip rats, the effects of amlodipine (1 mg/kg), telmisartan (6 mg/kg) and their combination on BP reduction were observed. In the chronic study, spontaneously hypertensive rats were treated with amlodipine (1 mg/kg), telmisartan (6 mg/kg), and their combination for 4 months. Histopathologic examinations were performed after the determination of BP and BP variability. RESULTS: There is a synergistic interaction between amlodipine and telmisartan on BP reduction. The optimal dose ratio was found at 1:6. The synergistic effect of this dose ratio (1:6) was also seen in two-kidney, one-clip rats. Long-term treatment with this combination results in a beneficial effect on the reduction of BP and BP variability. The end-organ damage, including myocardial hypertrophy, glomerular atrophy, and fibrosis, was significantly attenuated by this combination. CONCLUSION: The optimal dose ratio of amlodipine and telmisartan on BP was 1:6. This combination is beneficial for the BP and BP variability reduction and end-organ damage prevention.

Dysfunction of the cholinergic anti-inflammatory pathway mediates organ damage in hypertension.

Inflammatory responses are associated with the genesis and progression of end-organ damage (EOD) in hypertension. A role for the α7 nicotinic acetylcholine receptor (α7nAChR) in inflammation has recently been identified. We tested the hypothesis that α7nAChR dysfunction contributes to hypertensive EOD. In both spontaneously hypertensive rats (SHRs) and rats with abdominal aorta coarctation-induced hypertension, atropine-induced tachycardia was blunted compared with normotensive controls. Both models of hypertension were associated with deficits in expression of the vesicular acetylcholine transporter and the α7nAChR in cardiovascular tissues. In hypertension induced by abdominal aorta coarctation, deficits in aortic vesicular acetylcholine transporter and α7nAChR were present both above and below the coarctation site, indicating that they were independent of the level of arterial pressure itself. Hypertension in 40-week-old SHRs was associated with cardiac and aortic hypertrophy. Morphological abnormalities consistent with EOD, along with elevated tissue levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) were observed in the heart, kidney, and aorta. Chronic treatment of SHRs with the α7nAChR agonist PNU-282987 relieved EOD and inhibited tissue levels of proinflammatory cytokines and activation of nuclear factor κB. Greater serum levels of proinflammatory cytokines and more severe damage in the heart, aorta, and kidney were seen in α7nAChR(-/-) mice subjected to 2-kidney-1-clip surgery than in wild-type mice. A deficit in the cholinergic anti-inflammatory pathway appears to contribute to the pathogenesis of EOD in models of hypertension of varying etiology. This pathway may provide a new target for preventing cardiovascular disease resulting from hypertension.

The features of reserpine-induced gastric mucosal lesions.

AIM: To reinvestigate the characteristics of reserpine-induced gastric mucosal lesions (GMLs). METHODS: The GML-inducing effect of reserpine and the time-course of recovery from reserpine-induced GMLs were examined in Sprague-Dawley (SD) rats. The GML-inducing and blood pressure-decreasing effects of Compound Hypotensive Tablets (CHTs) were investigated in spontaneously hypertensive rats (SHRs). Intracerebroventricular (icv) injection and vagotomy were performed to verify the central vagal mechanism in reserpine-induced GMLs. RESULTS: Single intraperitoneal (ip) injections of reserpine (0.25, 0.5, 1, 2, 4, and 6 mg/kg) dose-dependently induced GMLs in SD rats. Both single and repeated (2 weeks) oral administrations of reserpine led to slight GMLs at doses of 24 mg/kg and 10 mg/kg, respectively. Blood pressure was significantly decreased in SHRs after 2 months of CHT administration (0.01 and 0.03 mg/kg; doses were expressed as the amount of reserpine in the CHT). CHT doses of 0.3 mg/kg induced GMLs, but 0.1 mg/kg did not. Examining the time course of recovery from GMLs, severe GMLs occurred 18 h after ip reserpine (4 mg/kg), obviously lessened at 1 week and healed spontaneously at 3 weeks. Intracerebroventricular injections of reserpine caused GMLs at much lower doses (0.08 and 0.4 mg/kg), and reserpine-induced GMLs were greatly inhibited by vagotomy, suggesting the involvement of a central vagal mechanism. CONCLUSION: Reserpine-induced GMLs were dose-dependent, and the lesions healed spontaneously within 3 weeks. Long-term treatment with CHT at doses adequate to decrease blood pressure will not induce GMLs. A central vagal mechanism was involved in reserpine-induced GMLs.

Blood pressure reduction combining baroreflex restoration for stroke prevention in hypertension in rats.

Blood pressure reduction is an important and effective strategy in stroke prevention in hypertensives. Recently, we found that baroreflex restoration was also crucial in stroke prevention. The present work was designed to test the hypothesis that a combination of blood pressure reduction and baroreflex restoration may be a new strategy for stroke prevention. In Experiment 1, the effects of ketanserin (0.3, 1, 3, 10 mg/kg), amlodipine (0.3, 1, 2, 3 mg/kg) and their combination (1 + 0.3, 1 + 1, 1 + 2, 1 + 3 mg/kg) on blood pressure and baroreflex sensitivity (BRS) of stroke-prone spontaneously hypertensive rats (SHR-SP) were determined under conscious state. It was found that both amlodipine and ketanserin decreased blood pressure dose-dependently. Ketanserin enfanced BRS from a very small dose but amlodipine enfanced BRS only at largest dose used. At the dose of 1 + 2 mg/kg (ketanserin + amlodipine), the combination possessed the largest synergism on blood pressure reduction. In Experiments 2 and 3, SHR-SP and two-kidney, two-clip (2K2C) renovascular hypertensive rats received life-long treatments with ketanserin (1 mg/kg) and amlodipine (2 mg/kg) or their combination (0.5 + 1, 1 + 2, 2 + 4 mg/kg). The survival time was recorded and the brain lesion was examined. It was found that all kinds of treatments prolonged the survival time of SHR-SP and 2K2C rats. The combination possessed a significantly better effect on stroke prevention than mono-therapies. In conclusion, combination of blood pressure reduction and baroreflex restoration may be a new strategy for the prevention of stroke in hypertension.

A systematic review of angiotensin receptor blockers in preventing stroke.

BACKGROUND AND PURPOSE: Angiotensin receptor blockers are widely used in patients at high risk of cardiocerebrovascular events. The aim of this meta-analysis was to investigate the effects of angiotensin receptor blockers on the risk of stroke. METHODS: Electronic searches of MEDLINE, EMBASE, and the Cochrane central register of controlled trials were performed. A total of 20 randomized clinical trials with 108 286 patients reporting stroke were available for this clinical outcome analysis. RESULTS: Angiotensin receptor blockers were associated with a significant reduction in the risk of stroke than placebo with an OR of 0.91 (0.84 to 0.98). Angiotensin receptor blockers were associated with no significant reduction in the risk of stroke compared with angiotensin-converting enzyme inhibitors (OR, 0.93; 0.84 to 1.03) and calcium antagonists (OR, 1.16; 0.91 to 1.48). CONCLUSIONS: Evidence of the benefit of angiotensin receptor blockers on the risk of stroke is provided when compared with placebo. There was no evidence of the benefit when comparing angiotensin receptor blockers with angiotensin-converting enzyme inhibitors and with calcium antagonists.

Effects of allisartan, a new AT(1) receptor blocker, on blood pressure and end-organ damage in hypertensive animals.

AIM: To investigate the effects of allisartan, a new angiotensin II type 1 (AT(1)) receptor antagonist, on blood pressure (BP) and end-organ damage (EOD) in hypertensive rats and dogs. METHODS: First, a single dose of allisartan was given intragastrically to evaluate the BP reduction in spontaneously hypertensive rats (SHRs), two kidney-one clip (2K1C) renovascular hypertensive rats and dogs, and Beagle dogs with angiotensin II-induced hypertension. Second, allisartan was mixed in rat chow for long-term treatment. After 4 months of drug administration, rats were instrumented to determine BP and baroreflex sensitivity (BRS). Observation of morphologic changes was used to estimate EOD. Third, the acute toxicity of allisartan was compared with that of losartan in mice. RESULTS: BP was significantly decreased after intragastric administration of allisartan in SHRs, 2K1C rats, 2K1C dogs and Beagle dogs with angiotensin II-induced hypertension. Compared with the control, SHRs that received long-term treatment with allisartan exhibited an improved BRS and organ protective effects. Mice who were administered allisartan experienced less acute toxicity than those treated with losartan. CONCLUSION: Allisartan is highly effective for BP reduction and organ protection with low toxicity.

Clonidine, moxonidine, folic acid, and mecobalamin improve baroreflex function in stroke-prone, spontaneously hypertensive rats.

AIM: To investigate the effect of clonidine, moxonidine, folic acid, and mecobalamin on arterial baroreflex (ABR) function in stroke-prone spontaneously hypertensive rats (SHR-SP) and the possible mechanisms involved. METHODS: Eighty-one SHR-SP were divided into 7 groups. Four groups were designated for the intragastric (ig) administration of clonidine (1.0 and 10.0 microg/kg), moxonidine (0.1 and 1.0 mg/kg), folic acid (1.0 mg/kg), and mecobalamin (1.0 mg/kg). Three groups were for the intracerebroventricular (icv) injection of clonidine (4 microg/4 microL), moxonidine (5 microg/4 microL), and mecobalamin (20 microg/4 microL). Blood pressure (BP) was recorded in the conscious state for 30 min and baroreflex sensitivity (BRS) was determined respectively before and after drug administration. RESULTS: Clonidine and moxonidine significantly decreased BP, prolonged the heart period (HP), and increased BRS when administered as either ig or icv injections. Both BP and HP were unchanged by ig folic acid or mecobalamin injection. However, BRS was significantly increased by both. CONCLUSION: Clonidine, moxonidine, folic acid, and mecobalamin improved impaired ABR function in SHR-SP. The central mechanism was involved in this effect of either clonidine or moxonidine. Mecobalamin improved ABR function through the peripheral mechanism.

Arterial baroreflex: a novel target for preventing stroke in rat hypertension.

BACKGROUND AND PURPOSE: Arterial baroreflex is one of the most important mechanisms in the regulation of cardiovascular activities. Arterial baroreflex function can be expressed as baroreflex sensitivity (BRS). The present study was designed to test 2 hypotheses: (1) BRS is a new independent predictor for the incidence of stroke in hypertension, and (2) restoration of BRS can prevent stroke in hypertension. METHODS: First, 82 stroke-prone spontaneously hypertensive rats (SHR-SP) aged 28 to 30 weeks were used. After measuring blood pressure and BRS, the survival time was observed. Second, 12 SHR-SP aged 8 months were used. Blood pressure and BRS were determined separately before and after intragastric administration of ketanserin (0.3 and 3.0 mg/kg). Third, SHR-SP aged 5 months were treated with ketanserin for 12 weeks (0.3 mg and 3.0 mg/kg per day). At the end of the treatment, blood pressure and BRS were determined and the end-organ damage was evaluated. Last, SHR-SP aged 3 months were treated with ketanserin (0.3 and 3.0 mg/kg per day) for life and the survival time was recorded. RESULTS: Stroke was significantly delayed in rats with high BRS than those with low BRS (time to 50% death was 1.47-fold longer than low BRS group; P<0.01). Ketanserin of 3.0 mg/kg per day decreased blood pressure and enhanced BRS, whereas 0.3 mg/kg per day only enhanced the BRS. Fatal stroke incidences were markedly reduced by treatment with both doses (P<0.0001 versus control group). CONCLUSIONS: The present study provides evidence that BRS is an independent predictor for stroke in hypertension. Restoration of BRS may be a new strategy for the prevention of stroke.