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There is a lack of valid animal models that mimic associations among multiple cardiovascular risk factors in humans. The present study developed an animal model that uses multiple cardiovascular risk factors\u2014namely, hypertension, hypothyroidism, and a high-fat diet (HFD). Two models of hypertension were used: renovascular hypertension (two-kidney, one clip [2K1C]) and spontaneously hypertensive rats (SHRs). The naive group was composed of normotensive rats. Twelve weeks after surgery to induce renovascular hypertension, rats in the 2K1C and SHR groups underwent thyroidectomy. The HFD was then implemented for 6 weeks. Renal function, serum redox status, biochemical CVD markers, electrocardiographic profile, blood pressure, mesenteric vascular bed reactivity, histopathology, and morphometry were investigated. Both experimental models induced dyslipidemia, renal function impairment, and hepatic steatosis, accompanied by higher levels of different inflammatory markers and serum oxidative stress. These alterations contributed to end-organ damage in all hypertensive rats. Our findings corroborate a viable alternative model that involves multiple cardiovascular risk factors and resembles conditions that are seen in humans. Both models mimicked CVD, but our data show that SHRs exhibit more significant pathophysiological changes.<\/jats:p>","DOI":"10.3390\/ph15070853","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T23:02:01Z","timestamp":1657666921000},"page":"853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A New Approach for the Development of Multiple Cardiovascular Risk Factors in Two Rat Models of Hypertension"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0725-7805","authenticated-orcid":false,"given":"Karyne Garcia Tafarelo","family":"Moreno","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFAC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline Aparecida Macedo","family":"Marques","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFAC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8449-3620","authenticated-orcid":false,"given":"Gabriela Pereira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFAC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth\u00e2nia Rosa","family":"Louren\u00e7one","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFAC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara Soligo","family":"Fortini","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFAC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia Regina Ter\u00e7o","family":"Leite","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFAC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariany Carvalho","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Histopathology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roosevelt Isa\u00edas Carvalho","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Histopathology, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila Isabel","family":"da Siva","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Biotechnology Applied to Agriculture, Paranaense University, Umuarama 87502-210, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-5098","authenticated-orcid":false,"given":"Arquimedes","family":"Gasparotto Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFAC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/S0140-6736(18)32203-7","article-title":"Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"Roth","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1332","DOI":"10.1016\/S2214-109X(19)30318-3","article-title":"World Health Organization cardiovascular disease risk charts: Revised models to estimate risk in 21 global regions","volume":"7","author":"Kaptoge","year":"2019","journal-title":"Lancet Glob. 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