Furthermore, pre-incubation with linopirdine reduced forskolin (cAMP activator)-induced vasorelaxation ACP-196 molecular weight in basilar while not altering forskolin-induced vasorelaxation of the LAD, suggesting that Kv7 channels play a more prominent role in the cerebral than coronary circulation. Consistent with the vessel data, whole cell Kv7 currents in cerebral VSMCs were potentiated by retigabine and inhibited by linopirdine,
while these responses were blunted in coronary VSMCs. This study provides evidence that mouse Kv7 channels may contribute differently to regulating the functional properties of cerebral and coronary arteries. Such heterogeneity has important implications for developing novel therapeutics for cardiovascular dysfunction. This article is protected by copyright. All rights reserved. “
“Please cite this paper as: Li X, Song Y, Han Y, Wang D, Zhu Y. Liver X receptor agonist MI-503 nmr alleviated high glucose-induced endothelial progenitor cell dysfunction via inhibition of reactive oxygen species and activation of AMP-activated protein kinase. Microcirculation 19: 547–553, 2012. Objective: Liver X receptors (LXRs) are key regulators of cholesterol
homeostasis. Synthetic LXR agonists are anti-atherogenic and anti-inflammatory. However, the effect of LXR agonists on endothelial progenitor cell (EPC) function is largely unknown. Here, we explored the effect of the LXR agonist TO901317 (TO) on EPC biology and the underlying mechanisms. Methods: diglyceride Endothelial progenitor cells were cultured in mannitol or 30 mm glucose (high glucose) for 24 hours. For TO treatments, cells were pretreated with TO (10 μm) for 12 hours, then mannitol or high glucose was added for an additional 24 hours. EPCs
function, reactive oxygen species (ROS) release, and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) were analyzed. Results: TO could restore the high glucose-impaired adhesion and migration capacity of EPCs. High glucose impaired EPC-mediated angiogenesis, and TO reversed the impairment. TO also alleviated ROS release induced by high glucose. Western blot analysis revealed that high glucose downregulated the phosphorylation of AMPK and endothelial nitric oxide synthase, which could be reversed with TO treatment. Furthermore, inhibiting AMPK activation by compound C could abolish the protective effects of TO on EPCs. Conclusions: TO had a protective effect on EPCs under high glucose by inhibiting ROS release and activating AMPK. “
“To test the hypothesis that Ca2+ responses to GPCR activation are coordinated between neighboring ECs of resistance arteries. EC tubes were freshly isolated from superior epigastric arteries of C57BL/6 mice. Intercellular coupling was tested using microinjection of propidium iodide. Following loading with fluo-4 dye, intracellular Ca2+ responses to ACh were imaged with confocal microscopy.