{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:18:14Z","timestamp":1790230694031,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T00:00:00Z","timestamp":1547510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP18K06861"],"award-info":[{"award-number":["JP18K06861"]}]},{"name":"JSPS KAKENHI","award":["JP17K08318"],"award-info":[{"award-number":["JP17K08318"]}]},{"name":"JSPS KAKENHI","award":["JP18K06974"],"award-info":[{"award-number":["JP18K06974"]}]},{"name":"The Food Science Institute Foundation (Ryoushoku-kenkyukai)","award":["2018A12"],"award-info":[{"award-number":["2018A12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gut microbiota are emerging as potential contributors to the regulation of host homeostasis. Dysbiosis of the gut microbiota associated with increased intestinal permeability facilitates the passage of endotoxins and other microbial products, including indoxyl sulfate in the circulation. Although an emerging body of evidence has suggested that indoxyl sulfate is a key substance for the development of chronic kidney disease, few studies have investigated the direct association of indoxyl sulfate with vascular function. We hypothesized that indoxyl sulfate adversely affects vascular function. Aortas isolated from male Wistar rat were examined in the presence or absence of indoxyl sulfate to assess the vascular function, including vasorelaxation and vasocontraction. Indoxyl sulfate (vs. vehicle) (1) decreased vasorelaxation induced by acetylcholine (ACh) but not by sodium nitroprusside; (2) had no significant alterations of noradrenaline-induced vasocontraction in the absence and presence of endothelium; (3) decreased adenylyl cyclase activator (forskolin)-induced vasorelaxation, while such a difference was eliminated by endothelial denudation; and (4) decreased vasorelaxations induced by calcium ionophore (A23187) and transient receptor potential vanilloid 4 agonist (GSK1016790A). The indoxyl sulfate-induced decrease in the vasorelaxations induced by ACh and A23187 increased by cell-permeant superoxide dismutase or by organic anion transporter inhibitor. However, apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, had no effects on vasorelaxations induced by ACh, A23187, forskolin, and GSK1016790A in the presence of indoxyl sulfate. These results suggest that indoxyl sulfate directly affects the vascular function, particularly, endothelium-dependent vasorelaxation, and this effect may be attributable to increased oxidative stress after cell transportion via organic anion transporter, and such increased oxidative stress may not be attributable to activation of NADPH oxidase activation.<\/jats:p>","DOI":"10.3390\/ijms20020338","type":"journal-article","created":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T03:09:13Z","timestamp":1547608153000},"page":"338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Acute Exposure to Indoxyl Sulfate Impairs Endothelium-Dependent Vasorelaxation in Rat Aorta"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9177-8384","authenticated-orcid":false,"given":"Takayuki","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Takayanagi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihoka","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneo","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41467-017-00900-1","article-title":"The gut microbiome in atherosclerotic cardiovascular disease","volume":"8","author":"Jie","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrcardio.2016.183","article-title":"Role of gut microbiota in atherosclerosis","volume":"14","author":"Jonsson","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.2337\/db13-0844","article-title":"Assessing the human gut microbiota in metabolic diseases","volume":"62","author":"Karlsson","year":"2013","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4592","DOI":"10.1073\/pnas.1011383107","article-title":"Human oral, gut, and plaque microbiota in patients with atherosclerosis","volume":"108","author":"Koren","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1042\/CS20171107","article-title":"Altered microbiome in chronic kidney disease: Systemic effects of gut-derived uremic toxins","volume":"132","author":"Lau","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/nm.4358","article-title":"Gut microbiome and serum metabolome alterations in obesity and alter weight-loss intervention","volume":"23","author":"Liu","year":"2017","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1161\/CIRCRESAHA.117.309715","article-title":"Gut microbiota in cardiovascular health and disease","volume":"120","author":"Tang","year":"2017","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jnutbio.2017.12.010","article-title":"The gut microbiota as a novel regulator of cardiovascular function and disease","volume":"56","author":"Battson","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.phrs.2018.03.003","article-title":"Microbiota metabolites: Pivotal players of cardiovascular damage in chronic kidney disease","volume":"130","author":"Cosola","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/j.1525-139X.2009.00576.x","article-title":"Protein-bound toxins\u2014Update 2009","volume":"22","author":"Dou","year":"2009","journal-title":"Semin. Dial."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.lfs.2017.07.027","article-title":"Role of uremic toxin indoxyl sulfate in the progression of cardiovascular disease","volume":"185","author":"Gao","year":"2017","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.toxlet.2017.11.033","article-title":"Indoxyl sulfate accelerates vascular smooth muscle cell calcification via microRNA-29b dependent regulation of Wnt\/\u03b2-catenin signaling","volume":"284","author":"Zhang","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000365217","article-title":"Indoxyl sulfate induces IL-6 expression in vascular endothelial and smooth muscle cells through OAT3-mediated uptake and activation of AhR\/NF-\u03baB pathway","volume":"128","author":"Adelibieke","year":"2014","journal-title":"Nephron. Exp. Nephrol."},{"key":"ref_14","first-page":"95","article-title":"Crucial role of the aryl hydrocarbon receptor (AhR) in indoxyl sulfate-induced vascular inflammation","volume":"60","author":"Ito","year":"2016","journal-title":"J. Artheroscler. Thromb."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000447096","article-title":"Indoxyl sulfate downregulates Mas receptor via aryl hydrocarbon receptor\/nuclear factor-kappa B, and induces cell proliferation and tissue factor expression in vascular smooth muscle cells","volume":"133","author":"Ng","year":"2016","journal-title":"Nephron"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1038\/sj.ki.5000340","article-title":"Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells","volume":"69","author":"Yamamoto","year":"2006","journal-title":"Kidney Int."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yisireyili, M., Saito, S., Abudureyimu, S., Adelibieke, Y., Ng, H.Y., Nishijima, F., Takeshita, K., Murohara, T., and Niwa, T. (2014). Indoxyl sulfate-induced activation of (pro)renin receptor promotes cell proliferation and tissue factor expression in vascular smooth muscle cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109268"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"904","DOI":"10.5551\/jat.23663","article-title":"Aryl hydrocarbon receptor mediates indoxyl sulfate-induced cellular senescence in human umbilical vein endothelial cells","volume":"21","author":"Koizumi","year":"2014","journal-title":"J. Artheroscler. Thromb."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/1440-1681.12351","article-title":"Rosiglitazone attenuates indoxyl sulphate-induced endothelial dysfunction","volume":"42","author":"Chou","year":"2015","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1525-139X.2011.00925.x","article-title":"Vascular incompetence in dialysis patients\u2014Protein-bound uremic toxins and endothelial dysfunction","volume":"24","author":"Dou","year":"2011","journal-title":"Semin. Dial."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/ki.1994.98","article-title":"Effects of guanidine and uremic compounds on nitric oxide pathways","volume":"45","author":"MacAllister","year":"1994","journal-title":"Kidney Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1111\/j.1476-5381.2010.00802.x","article-title":"Differential sensitivity of basal and acetylcholine-induced activity of nitric oxide to blockade by asymmetric dimethylarginine in the rat aorta","volume":"160","author":"Craig","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1172\/JCI118771","article-title":"Vascular dysfunction in monkeys with diet-induced hyperhomocyst(e)inemia","volume":"98","author":"Lentz","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1038\/sj.bjp.0702374","article-title":"Investigation of the inhibitory effects of homocysteine and copper on nitric oxide-mediated relaxation of rat isolated aorta","volume":"126","author":"Emsley","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1161\/01.ATV.20.2.422","article-title":"Homocysteine-induced inhibition of endothelium-dependent relaxation in rabbit aorta: Role for superoxide anions","volume":"20","author":"Lang","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00424-013-1324-y","article-title":"Advanced glycation end products impair K(Ca)3.1- and K(Ca)2.3-mediated vasodilatation via oxidative stress in rat mesenteric arteries","volume":"466","author":"Zhao","year":"2014","journal-title":"Pflugers Arch."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jdiacomp.2012.08.007","article-title":"KB-R7943 restores endothelium-dependent relaxation induced by advanced glycosylation end products in rat aorta","volume":"27","author":"Su","year":"2013","journal-title":"J. Diabetes Complicat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1002\/jcp.25018","article-title":"Para-cresyl sulfate acutely impairs vascular reactivity and induces vascular remodeling","volume":"230","author":"Gross","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.atherosclerosis.2015.09.019","article-title":"Deleterious vascular effects of indoxyl sulfate and reversal by oral adsorbent AST-120","volume":"243","author":"Six","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1080\/10715762.2017.1296575","article-title":"Indoxyl sulfate potentiates endothelial dysfunction via reciprocal role for reactive oxygen species and RhoA\/ROCK signaling in 5\/6 nephrectomized rats","volume":"51","author":"Chu","year":"2017","journal-title":"Free Radic. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"30","DOI":"10.2215\/CJN.05340610","article-title":"Indoxyl sulfate-induced endothelial dysfunction in patients with chronic kidney disease via an induction of oxidative stress","volume":"6","author":"Yu","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"942","DOI":"10.3349\/ymj.2016.57.4.942","article-title":"AST-120 improves microvascular endothelial dysfunction in end-stage renal disease patients receiving hemodialysis","volume":"57","author":"Ryu","year":"2016","journal-title":"Yonsei Med. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/apha.12646","article-title":"Endothelial dysfunction and vascular disease\u2014A 30th anniversary update","volume":"219","author":"Vanhoutte","year":"2017","journal-title":"Acta. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1161\/CIRCRESAHA.116.306531","article-title":"Thirty Years of Saying NO: Sources, Fate, Actions, and Misfortunes of the Endothelium-Derived Vasodilator Mediator","volume":"119","author":"Vanhoutte","year":"2016","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/j.1476-5381.1996.tb15712.x","article-title":"Changes in superoxide dismutase mRNA expression by streptozotocin-induced diabetes","volume":"119","author":"Kamata","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1159\/000468542","article-title":"Role of organic anion transporters in the uptake of protein-bound uremic toxins by human endothelial cells and monocyte chemoattractant protein-1 expression","volume":"54","author":"Faveretto","year":"2017","journal-title":"J. Vasc. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1053\/j.jrn.2010.05.002","article-title":"Indoxyl sulfate is a nephron-vascular toxin","volume":"20","author":"Niwa","year":"2010","journal-title":"J. Ren. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1161\/CIRCRESAHA.111.243972","article-title":"Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system","volume":"110","author":"Lassegue","year":"2012","journal-title":"Circ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vph.2016.08.006","article-title":"Impact of apocynin on vascular disease in hypertension","volume":"87","author":"Virdis","year":"2016","journal-title":"Vascul. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.phrs.2016.12.017","article-title":"The opposing roles of NO and oxidative stress in cardiovascular disease","volume":"116","author":"Ritchie","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.lfs.2011.10.014","article-title":"Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells","volume":"90","author":"Lee","year":"2012","journal-title":"Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"C389","DOI":"10.1152\/ajpcell.00206.2009","article-title":"ROS and PDGF-beta [corrected] receptors are critically involved in indoxyl sulfate actions that promote vascular smooth muscle cell proliferation and migration","volume":"297","author":"Shimizu","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1124\/jpet.108.148718","article-title":"Eicosapentaenoic acid improves imbalance between vasodilator and vasoconstrictor actions of endothelium-derived factors in mesenteric arteries from rats at chronic stage of type 2 diabetes","volume":"329","author":"Matsumoto","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.freeradbiomed.2017.08.027","article-title":"Poly (I:C) impairs NO donor-induced relaxation by overexposure to NO via the NF-kappa B\/iNOS pathway in rat superior mesenteric arteries","volume":"112","author":"Ando","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.vph.2014.01.004","article-title":"PKA and Epac activation mediates cAMP-induced vasorelaxation by increasing endothelial NO production","volume":"60","author":"Cuinas","year":"2014","journal-title":"Vascul. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"C1552","DOI":"10.1152\/ajpcell.00534.2005","article-title":"Convergence of Ca2+-desensitizing mechanisms activated by forskolin and phenylephrine pretreatment, but not 8-bromo-cGMP","volume":"290","author":"Porter","year":"2006","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.bcp.2017.09.004","article-title":"The cAMP effectors PKA and Epac activate endothelial NO synthase through PI3K\/Akt pathway in human endothelial cells","volume":"145","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.cellsig.2009.01.038","article-title":"Forskolin increases angiogenesis through the coordinated cross-talk of PKA-dependent VEGF expression and Epac-mediated PI3K\/Akt\/eNOS signaling","volume":"21","author":"Namkoong","year":"2009","journal-title":"Cell Signal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/sj.bjp.0703572","article-title":"Mechanisms underlying the chronic pravastatin treatment-induced improvement in the impaired endothelium-dependent aortic relaxation seen in streptozotocin-induced diabetic rats","volume":"131","author":"Kobayashi","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ejphar.2017.03.062","article-title":"Impaired endothelium-derived hyperpolarization-type relaxation in superior mesenteric arteries isolated from female Otsuka Long-Evans Tokushima Fatty rats","volume":"807","author":"Matsumoto","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.3390\/toxins6061742","article-title":"Differential effects of indoxyl sulfate and inorganic phosphate in a murine cerebral endothelial cell line (bEnd.3)","volume":"6","author":"Stinghen","year":"2014","journal-title":"Toxins"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1053\/j.jrn.2007.10.013","article-title":"Oral sorbent AST-120 increases renal NO synthesis in uremic rats","volume":"18","author":"Tumur","year":"2008","journal-title":"J. Ren. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1159\/000191468","article-title":"Indoxyl sulfate inhibits nitric oxide production and cell viability by inducing oxidative stress in vascular endothelial cells","volume":"29","author":"Tumur","year":"2009","journal-title":"Am. J. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.diabres.2008.09.053","article-title":"Serum indoxyl sulfate levels in patients with diabetic nephropathy: Relation to renal function","volume":"83","author":"Atoh","year":"2009","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1900\/RDS.2010.7.275","article-title":"Increased levels of total P-Cresylsulphate and indoxyl sulphate are associated with coronary artery disease in patients with diabetic nephrophathy","volume":"7","author":"Chiu","year":"2010","journal-title":"Rev. Diabet. Stud."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/nep.13452","article-title":"Diet, gut microbiome and indoxyl sulfate in chronic kidney disease patients","volume":"23","author":"Yang","year":"2018","journal-title":"Nephrology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00787.2016","article-title":"Vasculopathy in the setting of cardiorenal syndrome: Roles of protein-bound uremic toxins","volume":"313","author":"Guo","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_58","first-page":"96","article-title":"Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis","volume":"124","author":"Niwa","year":"1994","journal-title":"J. Lab. Clin. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000189284","article-title":"Accumulation of indoxyl-beta-D-glucuronide in uremic serum: Suppression of its production by oral sorbent and efficient removal by hemodialysis","volume":"74","author":"Niwa","year":"1996","journal-title":"Nephron"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1159\/000452604","article-title":"Indoxyl sulfate impairs endothelial progenitor cells and might contribute to vascular dysfunction in patients with chronic kidney disease","volume":"41","author":"Lin","year":"2016","journal-title":"Kidney Blood Press Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/eurheartj\/ehp574","article-title":"Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes?","volume":"31","author":"Lekawanvijit","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Matsumoto, T., Kobayashi, S., Ando, M., Iguchi, M., Takayanagi, K., Kojima, M., Taguchi, K., and Kobayashi, T. (2017). Alteration of vascular responsiveness to uridine adenosine tetraphosphate in aortas isolated from male diabetic Otsuka Long-Evans Tokushima Fatty rats: The involvement of prostanoids. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112378"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1089\/rej.2016.1864","article-title":"Age-related reduction of contractile responses to urotensin II is seen in aortas from Wistar rats but not from type 2 diabetic Goto-Kakizaki rats","volume":"20","author":"Matsumoto","year":"2017","journal-title":"Rejuvenation Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11302-017-9595-y","article-title":"UDP-induced relaxation is enhanced in aorta from female obese Otsuka Long-Evans Tokushima Fatty rats","volume":"14","author":"Kobayashi","year":"2018","journal-title":"Purinergic Signal."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/2\/338\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:26:05Z","timestamp":1760185565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/2\/338"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,15]]},"references-count":64,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["ijms20020338"],"URL":"https:\/\/doi.org\/10.3390\/ijms20020338","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,15]]}}}