{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:44:45Z","timestamp":1788925485850,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan","award":["22H03514"],"award-info":[{"award-number":["22H03514"]}]},{"name":"Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan","award":["20C5"],"award-info":[{"award-number":["20C5"]}]},{"name":"the Salt Sciences Research Foundation","award":["22H03514"],"award-info":[{"award-number":["22H03514"]}]},{"name":"the Salt Sciences Research Foundation","award":["20C5"],"award-info":[{"award-number":["20C5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: The nonsteroidal mineralocorticoid receptor blocker esaxerenone is effective in reducing blood pressure (BP). Objective: In this study, we investigated esaxerenone-driven sodium homeostasis and its association with changes in BP in Dahl salt-sensitive (DSS) hypertensive rats. Methods: In the different experimental setups, we evaluated BP by a radiotelemetry system, and sodium homeostasis was determined by an approach of sodium intake (food intake) and excretion (urinary excretion) in DSS rats with a low-salt diet (0.3% NaCl), high-salt diet (HSD, 8% NaCl), HSD plus 0.001% esaxerenone (w\/w), and HSD plus 0.05% furosemide. Results: HSD-fed DSS rats showed a dramatic increase in BP with a non-dipper pattern, while esaxerenone treatment, but not furosemide, significantly reduced BP with a dipper pattern. The cumulative sodium excretion in the active period was significantly elevated in esaxerenone- and furosemide-treated rats compared with their HSD-fed counterparts. Sodium content in the skin, skinned carcass, and total body tended to be lower in esaxerenone-treated rats than in their HSD-fed counterparts, while these values were unchanged in furosemide-treated rats. Consistently, sodium balance tended to be reduced in esaxerenone-treated rats during the active period. Histological evaluation showed that esaxerenone, but not furosemide, treatment attenuated glomerulosclerosis, tubulointerstitial fibrosis, and urinary protein excretion induced by high salt loading. Conclusions: Collectively, these findings suggest that an esaxerenone treatment-induced reduction in BP and renoprotection are associated with body sodium homeostasis in salt-loaded DSS rats.<\/jats:p>","DOI":"10.3390\/ijms23168915","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T09:42:56Z","timestamp":1660124576000},"page":"8915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association of Antihypertensive Effects of Esaxerenone with the Internal Sodium Balance in Dahl Salt-Sensitive Hypertensive Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"Mai","family":"Hattori","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9172-5343","authenticated-orcid":false,"given":"Asadur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kidoguchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nourin","family":"Jahan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihide","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Life Science Research Center, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiko","family":"Morisawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6046-3785","authenticated-orcid":false,"given":"Hiroyuki","family":"Ohsaki","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2, Tomogaoka, Suma-ku, Kobe 654-0142, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8508-827X","authenticated-orcid":false,"given":"Hideki","family":"Kobara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5252-5138","authenticated-orcid":false,"given":"Akram","family":"Hossain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akumwami","family":"Steeve","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"},{"name":"Department of Anesthesiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5971-820X","authenticated-orcid":false,"given":"Akira","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1161\/HYPERTENSIONAHA.120.15153","article-title":"Trends in Hypertension-Related Cardiovascular Mortality in the United States, 2000 to 2018","volume":"76","author":"Rethy","year":"2020","journal-title":"Hypertension"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0002-9343(78)90045-1","article-title":"The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension","volume":"64","author":"Kawasaki","year":"1978","journal-title":"Am. 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