{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T23:23:21Z","timestamp":1768778601838,"version":"3.49.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>High fructose consumption increases blood pressure through microglia-related neuroinflammation in rats. Since intermediate-conductance calcium-activated potassium channels (KCa3.1) potentiates microglial reactivity, we examined whether the pretreatment with the KCa3.1 channel blocker TRAM-34 or minocycline prevents hypertension development in fructose-fed rats.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>The study involved male Wistar rats that were given either high fructose (10% in drinking water) or tap water for 21 days. Fructose groups also received minocycline or TRAM-34 systemically for 21 days. We measured systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) periodically with tail-cuff; proinflammatory cytokines, and insulin levels in plasma via Enzyme-linked immunosorbent assay (ELISA), and neuroinflammatory markers in the nucleus tractus solitarii (NTS) by qPCR at the end of 21 days. We also examined endothelium-dependent hyperpolarization (EDH)-type vasorelaxations in isolated mesenteric arteries of the rats ex vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>SBP, DBP, and HR increased in the fructose group. Both minocycline and TRAM-34 significantly prevented these increases. Fructose intake also increased plasma interleukin-6, interleukin-1\u03b2, tumor necrosis factor-\u03b1, and insulin levels, whereas pretreatment with TRAM-34 prevented these increases as well. Iba-1, but not cluster of differentiation-86 levels were significantly higher in the NTS samples of fructose-fed hypertensive rats which implied microglial proliferation. EDH-type vasorelaxations mediated by endothelial KCa3.1 attenuated in the fructose group; however, TRAM-34 did not cause further deterioration in the relaxations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>TRAM-34 is as effective as minocycline in preventing fructose-induced hypertension without interfering with EDH-type vasodilation. Furthermore, TRAM-34 relieves high fructose-associated systemic inflammation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpae115","type":"journal-article","created":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T15:39:36Z","timestamp":1724513976000},"page":"995-1002","source":"Crossref","is-referenced-by-count":1,"title":["The KCa3.1 Channel Blocker TRAM-34 and Minocycline Prevent Fructose-Induced Hypertension in Rats"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0470-9995","authenticated-orcid":false,"given":"Abdelrahman","family":"Hamad","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Hacettepe University , Ankara ,","place":["Turkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1339-2616","authenticated-orcid":false,"given":"Melike Hacer","family":"Ozkan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Hacettepe University , Ankara ,","place":["Turkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"2024122308305150700_CIT0001","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1161\/HYP.0000000000000084","article-title":"Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association","volume":"72","author":"Carey","year":"2018","journal-title":"Hypertension"},{"key":"2024122308305150700_CIT0002","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1152\/japplphysiol.00182.2010","article-title":"Point: chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension","volume":"109","author":"Esler","year":"2010","journal-title":"J Appl 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