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Given the prevalent use of polytherapy in treating most hypertensive patients, comprehending the time\u2010dependent effects of combination treatments on inflammation becomes imperative. In this study, spontaneously hypertensive rats (SHR) were divided into seven groups (<jats:italic>n<\/jats:italic>\u2009=\u20096): (i) SHR\u2009+\u2009vehicle, (ii) SHR\u2009+\u2009nebivolol, (iii) SHR\u2009+\u2009valsartan, (iv) SHR\u2009+\u2009lisinopril, (v) SHR\u2009+\u2009nebivolol\u2013valsartan, (vi) SHR\u2009+\u2009nebivolol\u2013lisinopril, and (vii) WKY\u2009+\u2009vehicle. Blood pressure was measured using the tail\u2010cuff method. Temporal alterations in inflammatory cytokines TNF\u2010\u03b1, IL\u20106, and IL\u201010 were assessed in serum through ELISA and mRNA expression in aortic tissue via qPCR after 1, 2, and 4\u2009weeks of treatment with nebivolol, lisinopril, valsartan, and their respective combinations. Histological alterations in the aorta were assessed. The findings indicated that combined treatments reduced systolic and diastolic blood pressure in SHR. The nebivolol and lisinopril combination demonstrated a significant decrease in IL\u20106 serum and mRNA expression at both 1\u2009week and 4\u2009weeks into the treatment. Additionally, TNF\u2010\u03b1 mRNA expression also showed a reduction with this combination at the same time points. Particularly, nebivolol\u2013valsartan significantly decreased TNF\u2010\u03b1 serum and mRNA expression after one and four weeks of treatment. Furthermore, an elevation in serum IL\u201010 levels was observed with both combination treatments starting from the second week onwards. This study provides compelling evidence that concurrent administration of nebivolol with lisinopril or valsartan exerts time\u2010dependent effects, reducing proinflammatory cytokines TNF\u2010\u03b1 and IL\u20106 while modifying IL\u201010 levels in an experimental hypertensive model.<\/jats:p>","DOI":"10.1002\/prp2.1189","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T05:05:41Z","timestamp":1710911141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Modulation of <scp>TNF<\/scp>\u2010\u03b1, interleukin\u20106, and interleukin\u201010 by nebivolol\u2013valsartan and nebivolol\u2013lisinopril polytherapy in <scp>SHR<\/scp> rats"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1899-3736","authenticated-orcid":false,"given":"Lezama\u2010Martinez","family":"Diego","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, FES Cuautitlan Universidad Nacional Autonoma de Mexico  Cuautitlan Izcalli Mexico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0431-5427","authenticated-orcid":false,"given":"Flores\u2010Monroy","family":"Jazmin","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, FES Cuautitlan Universidad Nacional Autonoma de Mexico  Cuautitlan Izcalli Mexico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5624-1693","authenticated-orcid":false,"given":"Ramirez\u2010Hernandez","family":"Diana","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, FES Cuautitlan Universidad Nacional Autonoma de Mexico  Cuautitlan Izcalli Mexico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2137-9315","authenticated-orcid":false,"given":"Garrido\u2010Farina","family":"German\u2010Isauro","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, FES Cuautitlan Universidad Nacional Autonoma de Mexico  Cuautitlan Izcalli Mexico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3853-6313","authenticated-orcid":false,"given":"Fonseca\u2010Coronado","family":"Salvador","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, FES Cuautitlan Universidad Nacional Autonoma de Mexico  Cuautitlan Izcalli Mexico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1439-523X","authenticated-orcid":false,"given":"Hernandez\u2010Campos","family":"Maria\u2010Elena","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Estudios de Posgrado e 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