{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:07:58Z","timestamp":1785859678093,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","award":["310719\/2023-2"],"award-info":[{"award-number":["310719\/2023-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Foundation for Research Support in the State of Bahia\u2014FAPESB","award":["PIE0001\/2024"],"award-info":[{"award-number":["PIE0001\/2024"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Arterial hypertension (AH) remains a global health concern due to its multifactorial etiology, limited therapeutic success, and high cardiovascular risk. In this context, plant-derived compounds such as essential oils have gained attention as alternative strategies. The monoterpene (-)-linalool (LIN) demonstrates antihypertensive effects. However, its clinical application is hampered by poor solubility and low bioavailability. Methods: This study aimed to investigate the chronic cardiovascular effects of free LIN and its inclusion complex with \u03b2-cyclodextrin (LIN\/\u03b2-CD) in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. Results: Pharmacokinetic analysis showed that complexation with \u03b2-CD markedly improved LIN plasma exposure, increasing systemic bioavailability by approximately 20-fold and prolonging its circulation time. In acute assays, intravenous LIN and LIN\/\u03b2-CD (50 mg\/kg) reduced blood pressure in SHR, LIN induced bradycardia, and LIN\/\u03b2-CD elicited a mild, non-significant tachycardia. Orally administered LIN\/\u03b2-CD exerted superior antihypertensive effects compared to free LIN. In a 60-day chronic regimen, LIN\/\u03b2-CD consistently maintained reduced arterial pressure, achieving levels comparable to normotensive controls, while free LIN produced transient effects. LIN\/\u03b2-CD also significantly reduced the cardiac mass index in SHR, suggesting attenuation of hypertrophic remodeling. Vascular reactivity assays revealed enhanced endothelium-dependent and -independent relaxation and diminished vasoconstriction in LIN\/\u03b2-CD-treated animals, indicating improved endothelial and smooth muscle function. Histological analyses confirmed the absence of cardiac or vascular injury in both treatment groups. Conclusions: In conclusion, the LIN\/\u03b2-CD complex improves the pharmacokinetic profile and enhances the arterial morphology, antihypertensive and cardioprotective effects of linalool. These findings support its translational potential as a safe and effective oral formulation for the long-term management of hypertension and associated cardiovascular dysfunction.<\/jats:p>","DOI":"10.3390\/ph19010037","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:05:22Z","timestamp":1766498722000},"page":"37","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Complexed Linalool with Beta-Cyclodextrin Improve Antihypertensive Activity: Pharmacokinetic and Pharmacodynamic Insights"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5403-3444","authenticated-orcid":false,"given":"Samuel","family":"Camargo","sequence":"first","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 41745-715, Brazil"},{"name":"Laboratory of Cardiovascular Physiology and Pharmacology, Federal University of Bahia, Salvador 40110-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8432-5045","authenticated-orcid":false,"given":"Carla","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliane","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Physiology and Pharmacology, Federal University of Bahia, Salvador 40110-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-2024","authenticated-orcid":false,"given":"Rafael Leonne","family":"Jesus","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Physiology and Pharmacology, Federal University of Bahia, Salvador 40110-902, 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Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Sergipe, Aracaju 49060-108, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5155-938X","authenticated-orcid":false,"given":"Lucindo","family":"Quintans-J\u00fanior","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Sergipe, Aracaju 49060-108, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8746-6449","authenticated-orcid":false,"given":"Darizy","family":"Silva","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 41745-715, Brazil"},{"name":"Laboratory of Cardiovascular 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