Objective To investigate the role and mechanism of platelet in the development of salt-sensitive hypertension.Methods 25 Dahl salt-sensitive rats (Dahl SS) were divided into three groups: low-salt diet (0.12% NaCl, LS), high-salt diet (8%NaCl, HS) and high-salt diet + platelet inhibitor (8%NaCl+busulfan, HS+bus).Blood pressures were measured by tail-cuff method.After six weeks, animals were sacrificed.Platelet p-selectin expression, platelet cytosolic Ca2+ concentration, platelet-leukocyte aggregation (PLA) in peripheral blood, and immune cells infiltrated on aortic walls were assessed by flow cytometry, and serum IL-6 level was tested by ELISA in vivo.Platelets purified from SD rats were treated with normal salt (0.9%NaCl) and high salt (1.3%NaCl), then the cytosolic Ca2+ concentration and p-selectin expression of platelet were detected.Results We found that Dahl SS rats with high-salt diet, relative to low-salt diet, presented with high blood pressure and increased the ratio of platelet p-selectin expression, Ca2+ concentration.IL-6 level and PLA in peripheral blood, and the number of infiltrated immune cells on aortic walls were also significantly elevated in high-salt diet group.The whole events were ameliorated by the platelet inhibitor busulfan.Cytosolic Ca2+ concentration and p-selectin expression were also increased in purified platelets treated with high salt than those treated with low salt (P < 0.05).Conclusions Our findings suggest that high salt induced platelet activation with increased Ca2+ concentration may play an important role in the development of salt-sensitive hypertension via vascular inflammation.However, the detailed mechanisms of platelet activation and development of high blood pressure via inflammation induced by high salt intake remain to be determined.

Objective To determine whether dopamine D5 receptor (D5R) regulates the development of dilated cardiomyopathy (DCM) by inhibiting oxidative stress.Methods We developed heart-specific hD5 mutant (α-MHC-hD5F173L) and wild type (α-MHC-hD5WT) transgenic mice.The NOX2 expression and ROS production were tested in the transgenic mice at three month of age.The α-MHC-hD5F173L mice were treated with either NADPH oxidase inhibitor Apocynin (1mmol/kg/day) or phosphate-buffered saline (PBS) as control by intraperitoneal injection for 4 weeks.After then, the indexes of heart function were measured.The hD5WT and hD5F173L were transfected respectively in rat H9C2 cells, in which ROS production and NOX2 expression were detected at basal level.Results The ROS production and NOX2 expression were higher in the heart of α-MHC-hD5F173L than α-MHC-hD5WT mice.Apocynin treatment improved the heart function of α-MHC-hD5F173L mice.NOX2 expression and ROS production were higher in hD5F173L than hD5WT transfected H9C2 cells.Conclusions Dopomine D5 receptor may prevent DCM development by inhibiting oxidative stress.

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.