{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:28:52Z","timestamp":1790162932645,"version":"4.1.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T00:00:00Z","timestamp":1573084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0223914","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T18:51:50Z","timestamp":1573152710000},"page":"e0223914","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sildenafil citrate long-term treatment effects on cardiovascular reactivity in a SHR experimental model of metabolic syndrome"],"prefix":"10.1371","volume":"14","author":[{"given":"Yosra","family":"Doghri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Chetaneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moez","family":"Rhimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aicha","family":"Kriaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Lalanne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Thorin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Maguin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Yassine","family":"Mallem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Desfontis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,11,7]]},"reference":[{"key":"pone.0223914.ref001","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/nyas.12030","article-title":"What is metabolic syndrome, and why are children getting it?","volume":"1281","author":"R Weiss","year":"2013","journal-title":"Ann N Y Acad Sci"},{"issue":"4","key":"pone.0223914.ref002","doi-asserted-by":"crossref","first-page":"e35739","DOI":"10.1371\/journal.pone.0035739","article-title":"Connection between telomerase activity in PBMC and markers of inflammation and endothelial dysfunction in patients with metabolic syndrome","volume":"7","author":"E Rentoukas","year":"2012","journal-title":"PLoS ONE"},{"issue":"3","key":"pone.0223914.ref003","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1515\/hmbci-2015-0039","article-title":"The study of markers of endothelial dysfunction in metabolic syndrome","volume":"24","author":"AK Ahirwar","year":"2015","journal-title":"Horm Mol Biol Clin Investig"},{"issue":"4","key":"pone.0223914.ref004","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.2337\/db06-0883","article-title":"Chronic treatment with sildenafil improves energy balance and insulin action in high fat-fed conscious mice","volume":"56","author":"JE Ayala","year":"2007","journal-title":"Diabetes"},{"issue":"1","key":"pone.0223914.ref005","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41387-018-0026-0","article-title":"Effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice","volume":"8","author":"K Johann","year":"2018","journal-title":"Nutr Diabetes"},{"issue":"5","key":"pone.0223914.ref006","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.jsxm.2016.02.166","article-title":"Efficacy and Safety of Sildenafil by Age in Men With Erectile Dysfunction","volume":"13","author":"I Goldstein","year":"2016","journal-title":"J Sex Med"},{"issue":"1","key":"pone.0223914.ref007","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.bpg.2013.03.007","article-title":"Diabetes, obesity and gut microbiota","volume":"27","author":"A Everard","year":"2013","journal-title":"Best Pract Res Clin Gastroenterol"},{"issue":"43","key":"pone.0223914.ref008","doi-asserted-by":"crossref","first-page":"16079","DOI":"10.3748\/wjg.v20.i43.16079","article-title":"Gut microbiota and metabolic syndrome","volume":"20","author":"D Festi","year":"2014","journal-title":"World J Gastroenterol"},{"issue":"20","key":"pone.0223914.ref009","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aao1603","article-title":"Causal effects of the microbiota on immune-mediated diseases","volume":"3","author":"JL Round","year":"2018","journal-title":"Sci Immunol"},{"key":"pone.0223914.ref010","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13578-017-0183-1","article-title":"Gut microbiota as a potential target of metabolic syndrome: the role of probiotics and prebiotics","volume":"7","author":"M He","year":"2017","journal-title":"Cell Biosci"},{"issue":"9","key":"pone.0223914.ref011","doi-asserted-by":"crossref","first-page":"984","DOI":"10.2174\/0929867324666171009121702","article-title":"Gut Microbiota as a Therapeutic Target for Metabolic Disorders","volume":"25","author":"H Okubo","year":"2018","journal-title":"Curr Med Chem"},{"issue":"7","key":"pone.0223914.ref012","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1089\/met.2017.0163","article-title":"Altered Gut Microbiota: A Link Between Diet and the Metabolic Syndrome","volume":"16","author":"MT Velasquez","year":"2018","journal-title":"Metab Syndr Relat Disord"},{"issue":"6","key":"pone.0223914.ref013","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/dmrr.2617","article-title":"Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes","volume":"31","author":"C Bleau","year":"2015","journal-title":"Diabetes Metab Res Rev"},{"issue":"29","key":"pone.0223914.ref014","doi-asserted-by":"crossref","first-page":"8787","DOI":"10.3748\/wjg.v21.i29.8787","article-title":"Role of the normal gut microbiota","volume":"21","author":"SM Jandhyala","year":"2015","journal-title":"World J Gastroenterol"},{"issue":"4","key":"pone.0223914.ref015","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/wsbm.1223","article-title":"Cyclic nucleotide signaling in intestinal epithelia: getting to the gut of the matter","volume":"5","author":"N Arshad","year":"2013","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"pone.0223914.ref016","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev-med-052914-091923","article-title":"New Pharmacological Strategies to Increase cGMP","volume":"67","author":"A Buglioni","year":"2016","journal-title":"Annu Rev Med"},{"issue":"4","key":"pone.0223914.ref017","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1159\/000279307","article-title":"Chronic sildenafil treatment corrects endothelial dysfunction and improves hypertension","volume":"31","author":"K Yaguas","year":"2010","journal-title":"Am J Nephrol"},{"issue":"2","key":"pone.0223914.ref018","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.vascn.2006.05.006","article-title":"Isolated heart perfusion according to Langendorff\u2014still viable in the new millennium","volume":"55","author":"M Skrzypiec-Spring","year":"2007","journal-title":"J Pharmacol Toxicol Methods"},{"issue":"1\u20133","key":"pone.0223914.ref019","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ejphar.2010.07.003","article-title":"Positive influence of AT(1) receptor antagonism upon the impaired celiprolol-induced vasodilatation in aorta from spontaneously hypertensive rats","volume":"644","author":"F Sauvaget","year":"2010","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"pone.0223914.ref020","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.idairyj.2014.05.004","article-title":"Vasorelaxant effects of camel and bovine casein hydrolysates in rat thoracic aorta and mesenteric artery","volume":"39","author":"H Kanso","year":"2014","journal-title":"International Dairy Journal"},{"issue":"3","key":"pone.0223914.ref021","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1211\/jpp.62.03.0008","article-title":"Nonlinear mixed effects models applied to cumulative concentration-response curves","volume":"62","author":"C Thorin","year":"2010","journal-title":"J Pharm Pharmacol"},{"key":"pone.0223914.ref022","first-page":"289","article-title":"Controlling the false discovery rate: A Practical and powerful approach to multiple testing","volume":"57","author":"Y Benjamini","year":"1995","journal-title":"JRoyStatistSoc"},{"issue":"2","key":"pone.0223914.ref023","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1159\/000278748","article-title":"Overfeeding-induced obesity in spontaneously hypertensive rats: an animal model of the human metabolic syndrome","volume":"56","author":"A Miesel","year":"2010","journal-title":"Ann Nutr Metab"},{"issue":"10","key":"pone.0223914.ref024","doi-asserted-by":"crossref","DOI":"10.3390\/nu10101502","article-title":"High Fat\/High Glucose Diet Induces Metabolic Syndrome in an Experimental Rat Model","volume":"10","author":"S Moreno-Fern\u00e1ndez","year":"2018","journal-title":"Nutrients"},{"issue":"Supplementum 3","key":"pone.0223914.ref025","doi-asserted-by":"crossref","first-page":"S401","DOI":"10.33549\/physiolres.933440","article-title":"Effect of deuterium-depleted water on selected cardiometabolic parameters in fructose-treated rats","volume":"65","author":"R Rehakova","year":"2016","journal-title":"Physiol Res"},{"key":"pone.0223914.ref026","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12986-016-0123-9","article-title":"Animal models of metabolic syndrome: a review","volume":"13","author":"SK Wong","year":"2016","journal-title":"Nutr Metab (Lond)"},{"issue":"3","key":"pone.0223914.ref027","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1124\/jpet.105.098798","article-title":"Hypercholesterolemia does not alter endothelial function in spontaneously hypertensive rats","volume":"317","author":"B Lorkowska","year":"2006","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"pone.0223914.ref028","doi-asserted-by":"crossref","first-page":"41","DOI":"10.5534\/wjmh.17028","article-title":"Udenafil, a Phosphodiesterase 5 Inhibitor, Reduces Body Weight in High-Fat-Fed Mice","volume":"36","author":"SY Ryu","year":"2018","journal-title":"World J Mens Health"},{"issue":"2","key":"pone.0223914.ref029","doi-asserted-by":"crossref","first-page":"E215","DOI":"10.1152\/ajpendo.00098.2010","article-title":"Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats","volume":"299","author":"N Brandt","year":"2010","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"5","key":"pone.0223914.ref030","doi-asserted-by":"crossref","first-page":"e001001","DOI":"10.1161\/JAHA.114.001001","article-title":"Effect of phosphodiesterase inhibition on insulin resistance in obese individuals","volume":"3","author":"JE Ho","year":"2014","journal-title":"J Am Heart Assoc"},{"issue":"2","key":"pone.0223914.ref031","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.pharmthera.2010.02.002","article-title":"Sympathetic nervous activation in obesity and the metabolic syndrome\u2014causes, consequences and therapeutic implications","volume":"126","author":"GW Lambert","year":"2010","journal-title":"Pharmacol Ther"},{"key":"pone.0223914.ref032","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3389\/fphys.2014.00356","article-title":"The adrenergic system in cardiovascular pathophysiology: a translational science point of view","volume":"5","author":"G Rengo","year":"2014","journal-title":"Front Physiol"},{"issue":"7","key":"pone.0223914.ref033","doi-asserted-by":"crossref","first-page":"e241","DOI":"10.1097\/CCM.0000000000000999","article-title":"Modification of the \u03b2-Adrenoceptor Stimulation Pathway in Zucker Obese and Obese Diabetic Rat Myocardium","volume":"43","author":"C Jiang","year":"2015","journal-title":"Crit Care Med"},{"key":"pone.0223914.ref034","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1471-2261-13-51","article-title":"ACE-inhibition, but not weight reduction restores cardiomyocyte response to \u03b2-adrenergic stimulation in the metabolic syndrome","volume":"13","author":"I Nevelsteen","year":"2013","journal-title":"BMC Cardiovasc Disord"},{"issue":"3","key":"pone.0223914.ref035","first-page":"232","article-title":"Myocardial dysfunction and abnormalities in intracellular calcium handling in obese rats","volume":"97","author":"AP Lima-Leopoldo","year":"2011","journal-title":"Arq Bras Cardiol"},{"key":"pone.0223914.ref036","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.lfs.2019.03.074","article-title":"Chronic administration of sildenafil improves endothelial function in spontaneously hypertensive rats by decreasing COX-2 expression and oxidative stress","volume":"225","author":"JJ Teixeira-da-Silva","year":"2019","journal-title":"Life Sci"},{"issue":"2\u20133","key":"pone.0223914.ref037","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.vph.2007.05.003","article-title":"Vasorelaxation induced by the new nitric oxide donor cis-[Ru(Cl)(bpy)(2)(NO)](PF(6)) is due to activation of K(Ca) by a cGMP-dependent pathway","volume":"47","author":"CN Lunardi","year":"2007","journal-title":"Vascul Pharmacol"},{"issue":"4","key":"pone.0223914.ref038","doi-asserted-by":"crossref","first-page":"E544","DOI":"10.1152\/ajpendo.00337.2010","article-title":"Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP\/cGMP signaling pathway","volume":"299","author":"SA Andric","year":"2010","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"2","key":"pone.0223914.ref039","doi-asserted-by":"crossref","first-page":"209","DOI":"10.33549\/physiolres.933007","article-title":"Natriuretic peptide resistance of mesenteric arteries in spontaneous hypertensive rat is alleviated by exercise","volume":"65","author":"J Yu","year":"2016","journal-title":"Physiol Res"},{"issue":"3","key":"pone.0223914.ref040","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1476-5381.1992.tb09015.x","article-title":"Sympathoinhibitory effects of rilmenidine may be mediated by sites located below the brainstem","volume":"105","author":"F Sannajust","year":"1992","journal-title":"Br J Pharmacol"},{"issue":"4","key":"pone.0223914.ref041","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1111\/j.1476-5381.1993.tb13704.x","article-title":"Different effects of aspirin on blood pressure of spontaneously hypertensive rats (SHR) with high and spontaneously low levels of blood pressure","volume":"109","author":"M Schirner","year":"1993","journal-title":"Br J Pharmacol"},{"issue":"5","key":"pone.0223914.ref042","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11906-016-0646-5","article-title":"Role of Phosphodiesterase 5 and Cyclic GMP in Hypertension","volume":"18","author":"E Mergia","year":"2016","journal-title":"Curr Hypertens Rep"},{"issue":"6","key":"pone.0223914.ref043","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1152\/japplphysiol.01252.2003","article-title":"Exercise training improves aortic endothelium-dependent vasorelaxation and determinants of nitric oxide bioavailability in spontaneously hypertensive rats","volume":"96","author":"DA Graham","year":"2004","journal-title":"J Appl Physiol"},{"issue":"9","key":"pone.0223914.ref044","doi-asserted-by":"crossref","first-page":"E767","DOI":"10.1152\/ajpendo.00369.2015","article-title":"Toll-like receptor 4-induced endoplasmic reticulum stress contributes to impairment of vasodilator action of insulin","volume":"309","author":"J-A Kim","year":"2015","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"pone.0223914.ref045","doi-asserted-by":"crossref","first-page":"2502843","DOI":"10.1155\/2018\/2502843","article-title":"The Effect of Chronic NO Synthase Inhibition on the Vasoactive and Structural Properties of Thoracic Aorta, NO Synthase Activity, and Oxidative Stress Biomarkers in Young SHR","volume":"2018","author":"A Berenyiova","year":"2018","journal-title":"Oxid Med Cell Longev"},{"issue":"4","key":"pone.0223914.ref046","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/ijo.2017.284","article-title":"Alterations in gut microbiota associated with a cafeteria diet and the physiological consequences in the host","volume":"42","author":"JM Del Bas","year":"2018","journal-title":"Int J Obes (Lond)"},{"issue":"3","key":"pone.0223914.ref047","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/ijo.2017.225","article-title":"A new animal diet based on human Western diet is a robust diet-induced obesity model: comparison to high-fat and cafeteria diets in term of metabolic and gut microbiota disruption","volume":"42","author":"RC Bortolin","year":"2018","journal-title":"Int J Obes (Lond)"},{"key":"pone.0223914.ref048","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3389\/fmicb.2014.00190","article-title":"Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus","volume":"5","author":"I Moreno-Indias","year":"2014","journal-title":"Front Microbiol"},{"issue":"6","key":"pone.0223914.ref049","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1161\/HYPERTENSIONAHA.115.05315","article-title":"GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION","volume":"65","author":"T Yang","year":"2015","journal-title":"Hypertension"},{"issue":"5","key":"pone.0223914.ref050","doi-asserted-by":"crossref","first-page":"e0126931","DOI":"10.1371\/journal.pone.0126931","article-title":"Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters","volume":"10","author":"V Lecomte","year":"2015","journal-title":"PLoS ONE"},{"issue":"7","key":"pone.0223914.ref051","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance","volume":"56","author":"PD Cani","year":"2007","journal-title":"Diabetes"},{"issue":"3","key":"pone.0223914.ref052","doi-asserted-by":"crossref","first-page":"I","DOI":"10.1016\/j.orcp.2008.04.003","article-title":"High-fat diet-induced obesity is attenuated by probiotic strain Lactobacillus paracasei ST11 (NCC2461) in rats","volume":"2","author":"M Tanida","year":"2008","journal-title":"Obes Res Clin Pract"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0223914","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T12:48:05Z","timestamp":1721998085000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0223914"}},"subtitle":[],"editor":[{"given":"Frank T.","family":"Spradley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,11,7]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0223914","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,7]]}}}