15 research outputs found
Rosiglitazone Restores Endothelial Dysfunction in a Rat Model of Metabolic Syndrome through PPARĪ³- and PPARĪ“-Dependent Phosphorylation of Akt and eNOS
Vascular endothelial dysfunction has been demonstrated in metabolic syndrome (MS). Chronic administration of rosiglitazone ameliorates endothelial dysfunction through PPARĪ³-mediated metabolic improvements. Recently, studies suggested that single dose of rosiglitazone also has direct vascular effects, but the mechanisms remain uncertain. Here we established a diet-induced rat model of MS. The impaired vasorelaxation in MS rats was improved by incubating arteries with rosiglitazone for one hour. Importantly, this effect was blocked by either inhibition of PPARĪ³ or PPARĪ“. In cultured endothelial cells, acute treatment with rosiglitazone increased the phosphorylation of Akt and eNOS and the production of NO. These effects were also abolished by inhibition of PPARĪ³, PPARĪ“, or PI3K. In conclusion, rosiglitazone improved endothelial function through both PPARĪ³- and PPARĪ“-mediated phosphorylation of Akt and eNOS, which might help to reconsider the complex effects and clinical applications of rosiglitazone
Activation of TRPV1 by Dietary Capsaicin Improves Endothelium-Dependent Vasorelaxation and Prevents Hypertension
Some plant-based diets lower the cardiometabolic risks and prevalence of hypertension. New evidence implies a role for the transient receptor potential vanilloid 1 (TRPV1) cation channel in the pathogenesis of cardiometabolic diseases. Little is known about impact of chronic TRPV1 activation on the regulation of vascular function and blood pressure. Here we report that chronic TRPV1 activation by dietary capsaicin increases the phosphorylation of protein kinase A (PKA) and eNOS and thus production of nitric oxide (NO) in endothelial cells, which is calcium dependent. TRPV1 activation by capsaicin enhances endothelium-dependent relaxation in wild-type mice, an effect absent in TRPV1-deficient mice. Long-term stimulation of TRPV1 can activate PKA, which contributes to increased eNOS phosphorylation, improves vasorelaxation, and lowers blood pressure in genetically hypertensive rats. We conclude that TRPV1 activation by dietary capsaicin improves endothelial function. TRPV1-mediated increase in NO production may represent a promising target for therapeutic intervention of hypertension
Nanoassembly Film of Carboxylic Polyaniline with Photosensitive Diazoresin and Its Photoelectric Conversion Properties
Photoelectric Conversion Property of Covalent-Attached Multilayer Self-Assembled Films Fabricated from Diazoresin and Fullerol
Microtribologic Properties of a Covalently Attached Nanostructured Self-Assembly Film Fabricated from Fullerene Carboxylic Acid and Diazoresin
Micropatterns of Protein and Conducting Polymer Molecules Fabricated by Layer-by-Layer Self-Assembly and Photolithography Techniques
Superconductivity in Potassium-Doped Few-Layer Graphene
Here we report the successful synthesis of superconducting
potassium-doped
few-layer graphene (K-doped FLG) with a transition temperature of
4.5 K, which is 1 order of magnitude higher than that observed in
the bulk potassium graphite intercalation compound (GIC) KC<sub>8</sub> (<i>T</i><sub>c</sub> = 0.39 K). The realization of superconductivity
in K-doped FLG shows the potential for the development of new superconducting
electronic devices using two-dimensional (2D) graphene as a basis
material
SodiumāGlucose Cotransporter 2 Inhibitor Canagliflozin Antagonizes SaltāSensitive Hypertension Through Modifying Transient Receptor Potential Channels 3 Mediated Vascular Calcium Handling
Background Saltāsensitive hypertension is highly prevalent and associated with cardiorenal damage. Large clinical trials have demonstrated that SGLT2 (sodiumāglucose cotransporter 2) inhibitors exert hypotensive effect and cardiorenal protective benefits in patients with hypertension with and without diabetes. However, the underlying mechanism remains elusive. Methods and Results Dahl saltāsensitive rats and saltāinsensitive controls were fed with 8% highāsalt diet and some of them were treated with canagliflozin. The blood pressure, urinary sodium excretion, and vascular function were detected. Transient receptor potential channel 3 (TRPC3) knockout mice were used to explain the mechanism. Canagliflozin treatment significantly reduced highāsaltāinduced hypertension and this effect was not totally dependent on urinary sodium excretion in saltāsensitive hypertensive rats. Assay of vascular function and proteomics showed that canagliflozin significantly inhibited vascular cytoplasmic calcium increase and vasoconstriction in response to highāsalt diet. High salt intake increased vascular expression of TRPC3 in saltāsensitive rats, which could be alleviated by canagliflozin treatment. Overexpression of TRPC3 mimicked saltāinduced vascular cytosolic calcium increase in vitro and knockout of TRPC3 erased the antihypertensive effect of canagliflozin. Mechanistically, highāsaltāinduced activation of NCX1 (sodiumācalcium exchanger 1) reverse mode increased cytoplasmic calcium level and vasoconstriction, which required TRPC3, and this process could be blocked by canagliflozin. Conclusions We define a previously unrecognized role of TRPC3/NCX1 mediated vascular calcium dysfunction in the development of highāsaltāinduced hypertension, which can be improved by canagliflozin treatment. This pathway is potentially a novel therapeutic target to antagonize saltāsensitive hypertension