{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:50Z","timestamp":1784557250297,"version":"3.55.0"},"reference-count":144,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:p>\n                    Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists.\n                    <jats:italic>In vivo<\/jats:italic>\n                    release of S1P (100\u2013300\u2009\u00b5g\/kg\n                    <jats:sub>bw<\/jats:sub>\n                    ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1\/3 antagonist VPbib2319 decreased baseline and\/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50\u2009pg\/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely.\n                  <\/jats:p>","DOI":"10.1530\/joe-16-0550","type":"journal-article","created":{"date-parts":[[2017,10,2]],"date-time":"2017-10-02T21:30:20Z","timestamp":1506979820000},"page":"251-265","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":3,"title":["Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism"],"prefix":"10.1530","volume":"235","author":[{"given":"Stephan","family":"Werth","sequence":"first","affiliation":[{"name":"1Institute of Experimental and Clinical Pharmacology and Toxicology, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"M\u00fcller-Fielitz","sequence":"additional","affiliation":[{"name":"1Institute of Experimental and Clinical Pharmacology and Toxicology, University of L\u00fcbeck, L\u00fcbeck, Germany"},{"name":"2CBBM (Center of Brain, Behavior and Metabolism), L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Raasch","sequence":"additional","affiliation":[{"name":"1Institute of Experimental and Clinical Pharmacology and Toxicology, University of L\u00fcbeck, L\u00fcbeck, Germany"},{"name":"2CBBM (Center of Brain, Behavior and Metabolism), L\u00fcbeck, Germany"},{"name":"3DZHK (German Centre for Cardiovascular Research), partner site Hamburg\/Kiel\/L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref991","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0895-7061(02)02257-4","article-title":"Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects","volume":"15","year":"2002","journal-title":"American Journal of Hypertension"},{"key":"ref821","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.pharmthera.2007.04.006","article-title":"Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology","volume":"115","year":"2007","journal-title":"Pharmacology and Therapeutics"},{"key":"ref691","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1172\/JCI110438","article-title":"Decreased adrenal responsiveness to angiotensin II: a defect present in spontaneously hypertensive rats. 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