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We speculate that high phosphate (HP) impairs arterial vasodilation via the endothelium and explore potential underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Isolated vessel relaxation, endothelial function, glomerular filtration rate (GFR), oxidative stress status and protein expression were assessed in HP diet mice. Mitochondrial function and protein expression were assessed in HP\u2010treated human umbilical vein endothelial cells (HUVECs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High phosphate (1.3%) diet for 12\u00a0weeks impaired endothelium\u2010dependent relaxation in mesenteric arteries, kidney interlobar arteries and afferent arterioles; reduced GFR and the blood pressure responses to acute administration of acetylcholine. The PPAR\u03b1\/LKB1\/AMPK\/eNOS pathway was attenuated in the endothelium of mesenteric arteries from HP diet mice. The observed vasodilatory impairment of mesenteric arteries was ameliorated by PPAR\u03b1 agonist WY\u201014643. The phosphate transporter PiT\u20101 knockdown prevented HP\u2010mediated suppression of eNOS activity by impeding phosphorus influx in HUVECs. Endothelium cytoplasmic and mitochondrial reactive oxygen species (ROS) were increased in HP diet mice. Moreover HP decreased the expression of mitochondrial\u2010related antioxidant genes. Finally, mitochondrial membrane potential and PGC\u20101\u03b1 expression were reduced by HP treatment in HUVECs, which was partly restored by AMPK\u03b1 agonist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HP impairs endothelial function by reducing NO bioavailability via decreasing eNOS activity and increasing mitochondrial ROS, in which the AMPK\u2010related signalling pathways may play a key role.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.13595","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T02:30:13Z","timestamp":1607394613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["High phosphate impairs arterial endothelial function through AMPK\u2010related pathways in mouse resistance 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