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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Diuretics are widely used antihypertensive agents because of their potent natriuretic effects. However, in hypertension with excessive renin\u2013angiotensin\u2013aldosterone system (RAAS) activation, further volume depletion may aggravate target-organ injury. We investigated the effects of loop diuretics and mineralocorticoid receptor (MR) blockade on plasma volume (PV) and organ injury in angiotensin II (Ang II)-induced hypertension. Male Sprague\u2013Dawley rats were assigned to six groups (n = 6\/group) receiving Sham or Ang II with or without furosemide and spironolactone. PV was measured by indocyanine green (ICG) dilution, together with blood pressure, histological, immunohistochemical, and molecular assessments. Longitudinal data were analyzed by two-way repeated-measures ANOVA; animal-level endpoints by one-way ANOVA; histological and immunohistochemical measurements by nested one-way ANOVA; and two-group comparisons by unpaired t tests, with appropriate post hoc testing. Ang II reduced PV, whereas furosemide caused a further decline without additional blood pressure reduction, accompanied by aggravated fibrosis, endothelial impairment, and dysregulation of fibrosis-related proteins. Spironolactone attenuated PV contraction, lowered blood pressure, preserved endothelial integrity, alleviated fibrosis, and partially normalized molecular alterations. MR blockade was associated with attenuation of PV contraction and target-organ injury, supporting a potential relationship between PV homeostasis and organ protection during chronic loop diuretic treatment.<\/jats:p>","DOI":"10.3390\/ijms27188251","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:07:29Z","timestamp":1789574849000},"page":"8251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mineralocorticoid Receptor Blockade Mitigates Loop Diuretic-Exacerbated Plasma Volume Contraction and Target-Organ Fibrosis in Angiotensin II-Induced Hypertension"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8303-8132","authenticated-orcid":false,"given":"Junxian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Physiology & Biomedical Sciences, Ischemic\/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-0134","authenticated-orcid":false,"given":"Yin Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biomedical Sciences, Ischemic\/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"},{"name":"Yanbian University Hospital, Yanbian University, Yanji 133000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41569-023-00964-1","article-title":"Immune and inflammatory mechanisms in hypertension","volume":"21","author":"Guzik","year":"2024","journal-title":"Nat. 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