The protective effect of electroacupuncture on the renal cortex of SHRs: A metabonomic analysis

Hypertension affects multiple organs in the body during the development of the disease. The antihypertensive effect of acupuncture has been confirmed. How the protective effect of electroacupuncture on the renal cortex of the spontaneously hypertensive rat (SHR) is achieved has not yet been determined. The purpose of this study was to understand the impact of electroacupuncture on the blood pressure of SHRs and the impact on metabolites in the renal cortex, looking for potential differential metabolites and then proceeding to the next step of exploratory research. The experimental animals were divided into four groups: control group, model group, electroacupuncture group and losartan potassium group. Electroacupuncture on bilateral Taichong (LR3) and Zusanli (ST36) lasted for 3 weeks, and the renal cortex was collected for metabonomics research. UHPLC–MS was used to analyze the changes in the metabolic spectrum of renal cortex tissue. The results showed that electroacupuncture can significantly reduce the blood pressure of SHRs. A total of 12 metabolites changed significantly in the comparison between each group and the model group.The possible mechanism is that the primary bile acid biosynthesis, bile secretion, tryptophan metabolism and other metabolic pathways affect the renal cortex.     

Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular–Coerulear Excitatory Interactions

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α₁-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α₁-adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α₁-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α₁-adrenoceptor density in whole hypothalamus and the expression levels of α_1A-adrenoceptor mRNA in the PVN. The results showed that: (i) agonists microinjection increased systolic blood pressure and heart rate in normotensive eutrophic rats, but not in prenatally malnourished subjects; (ii) antagonists microinjection reduced hypertension and tachycardia in undernourished rats, but not in eutrophic controls; (iii) in undernourished animals, antagonist administration to one nuclei allowed the agonists recover full efficacy in the complementary nucleus, inducing hypertension and tachycardia; (iv) early undernutrition did not modify the number of α₁-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α_1A-adrenoceptor mRNA in the PVN. These results support the hypothesis that systolic pressure and heart rate are increased by tonic reciprocal paraventricular–coerulear excitatory interactions in prenatally undernourished young-adult rats.     

食盐与心血管结局

介绍了食盐与心血管结局关系的最新研究结果,食盐摄入量与心血管结局之间呈J形关系;低盐和高盐都增加心血管危险;不支持普遍减盐推荐。     

微量元素与高血压

论述了微量高血压的关系,着着讨论了铅、镉、硒、锌与高血压的关系。     

微量元素与高血压Ⅰ.高血压病人的元素含量异常

高血压是脑卒中和冠心病的主要危险因素，我国现有1．2亿人正受到高血压的威胁。大多数高血压是可以防治的。膳食防治高血压的本质是维持元素平衡或纠正破坏了的元素平衡关系。本文简述了我国高血压流行情况、不同血压水平的心脑血管病发病危险、血压与微量元素的相关关系、高血压患者的元素含量异常，以及高血压的元素食疗防治。附1图、33表、44篇参考文献。     

Flow dynamics analyses of pathophysiological liver lobules using porous media theory

Blood flow inside the liver plays a key role in hepatic functions, and abnormal hemodynamics are highly correlated with liver diseases. To date, the flow field in an elementary building block of the organ, the liver lobule, is difficult to determine experimentally in humans due to its complicated structure, with radially branched microvas-culature and the technical difficulties that derive from its geometric constraints. Here we established a set of 3D com-putational models for a liver lobule using porous media theory and analyzed its flow dynamics in normal, fibrotic, and cirrhotic lobules. Our simulations indicated that those approximations of ordinary flow in portal tracts (PTs) and the central vein, and of porous media flow in the sinusoidal network, were reasonable only for normal or fibrotic lobules. Models modified with high resistance in PTs and collateral vessels inside sinusoids were able to describe the flow fea-tures in cirrhotic lobules. Pressures, average velocities, and volume flow rates were profiled and the predictions compared well with experimental data. This study furthered our under-standing of the flow dynamics features of liver lobules and the differences among normal, fibrotic, and cirrhotic lobules.     

Impaired pulmonary blood flow distribution in congestive heart failure assessed using synchrotron radiation microangiography

Synchrotron radiation microangiography is a powerful tool for assessing adverse changes in pulmonary vessel density associated with primary pulmonary hypertension (PH). Congestive heart failure (CHF) leads to a `secondary' onset of PH, yet it is unknown whether secondary PH is also associated with reduced vessel density. This study utilized synchrotron radiation to assess both pulmonary vessel density and endothelial function in a Dahl rat model of CHF with secondary PH. High salt‐fed Dahl salt‐sensitive (Dahl‐S) and salt‐resistant (Dahl‐R) rats were anesthetized and microangiography was performed to assess the pulmonary vessel density and vascular responses to (i) sodium nitroprusside (5.0 µg kg^?1 min^?1), (ii) acetylcholine (3.0 µg kg^?1 min^?1) and (iii) ET‐1_A receptor blockade, BQ‐123 (1 mg kg^?1). Dahl‐S rats developed CHF and secondary PH as evident by endothelial dysfunction, impaired vasodilatory responses to acetylcholine, enhanced vasodilatory responses to BQ‐123 and extensive pulmonary vascular remodeling. Consequently, the pulmonary vessel density was adversely reduced. Interestingly, the etiology of secondary PH manifests with structural and functional changes that are comparable with that previously reported for primary PH. One important discrepancy, however, is that ET‐1 modulation of pulmonary vessels is most striking in vessels with a diameter range of 100–200 µm in secondary PH, in contrast to a range of 200–300 µm in primary PH. Such discrepancies should be considered in future studies investigating primary and secondary forms of PH.     

Synergistic therapeutic effects of Duzhong Jiangya Tablets and amlodipine besylate combination in spontaneously hypertensive rats using 1H-NMR- and MS-based metabolomics

Duzhong Jiangya Tablet (DJT) composed of Eucommia ulmoides Oliv. and several other traditional Chinese medicines is a Chinese herbal compound, which is clinically used to treat hypertension. The aim of this study was to evaluate the antihypertensive effect of DJT and amlodipine besylate (AB) on the synergistic treatment of spontaneously hypertensive rats (SHRs), and to explore its antihypertensive mechanism. The synergistic therapeutic effect of DJT in combination with AB on SHR was studied using two metabolomics methods based on mass spectrum (MS) and nuclear magnetic resonance. Metabolomics analysis of plasma, urine, liver, and kidney and the combination of orthogonal partial least squares discriminant analysis was performed to expose potential biomarkers. Then, the overall metabolic characteristics and related abnormal metabolic pathways in hypertensive rats were constructed. Blood pressure measurements showed that DJT combined with AB has better effects in treating hypertension than it being alone. A total of 30 biomarkers were identified, indicating that hypertension disrupted the balance of multiple metabolic pathways in the body, and that combined administration restored metabolite levels better than their administration alone. The changes of biomarkers revealed the synergistic therapeutic mechanism of DJT combined with AB, which provided a reference for the combination of Chinese and Western medicines.     

Rapid separation and binding configuration prediction of the components in Danshen decoction to endothelin A receptor using affinity chromatography and molecular dynamics simulation

As a famous traditional Chinese formula, Danshen Decoction has the potential to relieve the pain of pulmonary arterial hypertension patients, however, the functional components remain unknown. Herein, we reported a method to screen the functional components in Danshen Decoction targeting endothelin receptor A, an accepted target for the treatment of the disease. The receptor was functionalized on the macroporous silica gel through an epidermal growth factor receptor fusion tag and its covalent inhibitor. Using the affinity gel as the stationary phase, the bioactive compound was identified as salvianolic acid B by mass spectrometry. The binding kinetic parameter (dissociation rate constants k_d) of salvianolic acid B with the receptor was determined via peak profiling. Using the specific ligands of the receptor as probes, the binding configuration prediction of salvianolic acid B with the receptor was performed by molecular dynamics simulation. Our results indicated that salvianolic acid B is a potential bioactive compound in Danshen Decoction targeting the receptor. This work showed that receptor chromatography in combination with molecular dynamics simulation is applicable to predicting the binding kinetics and configuration of a ligand to a receptor, providing crucial insight for the rational design of drugs that recognize functional proteins.     

DSC examination of the esophagus after implantation of special stents,designed for the management of acute esophagus variceal bleeding

Massive bleeding from esophagus varices presents a life threatening complication of portal hypertension. No effective method of treatment is available until now, that would guarantee high grade of patient wellness during the conditioning and investigation phase until the definitive treatment could be introduced. The aim of this study was to evaluate the tissue response to esophagus stents - designed for manage acute variceal bleeding - in animal experiment. Self-expandable nitinol stents were introduced into the esophagus of six porcines. Another twelve porcines were undergone the same procedure, using the new biodegradable stents made of PDO (polydioxanon). Histological investigations of the stented esophagus segments were observed after 2 and 4 weeks at the first 12 animals. To monitor the time of stent degradation, histology were performed 7 and 12 weeks after the implantation in the biodegradable group (3–3 animals). Differential scanning calorimetric examination was performed in all esophagus samples. Focal erosion of the esophagus segments was more explicit in the nitinol group at the histology. On the 7^th week all of the biodegradable stent were in the stomach and on the 12^th week these were completely solved. DSC examination showed significant alterations in the structure of the esophagus in both stented group compared to the healthy control. This experiment showed that the new self-expandable stents are safety and suitable procedure without deterioration of the esophageal wall. According to our DSC results the thermal denaturation of intact esophagus, its mucosa and muscle fragments revealed significant differences compared to healthy sample in favour the new biodegradable stent. Safety and efficiency in the experimental model had encouraged us to apply this method successfully patients with bleeding esophagus varices. The long term goal is to show that stent placement could be an effective way of decreasing or stabilising the acute bleeding from ruptured esophagus varices in cirrhotic patients.