{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:15:53Z","timestamp":1790158553001,"version":"4.1.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:p> 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6( Z),15( Z)-dienoic acid (20-HEDE) prevented 5\u03b1-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M\/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M\/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14<jats:sup>\u2212\/\u2212<\/jats:sup> mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 \u00b1 1 vs. 15 \u00b1 1 \u03bcm) and M\/L (0.29 \u00b1 0.03 vs. 0.17 \u00b1 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12\u201320-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 \u00b1 4 vs. 92 \u00b1 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 \u00b1 1 vs. 16 \u00b1 1 \u03bcm; M\/L: 0.39 \u00b1 0.04 vs. 0.23 \u00b1 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. <\/jats:p>","DOI":"10.1152\/ajprenal.00292.2013","type":"journal-article","created":{"date-parts":[[2013,7,4]],"date-time":"2013-07-04T04:28:15Z","timestamp":1372912095000},"page":"F753-F763","source":"Crossref","is-referenced-by-count":30,"title":["20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension"],"prefix":"10.1152","volume":"305","author":[{"given":"Yan","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Pharmacology, New York Medical College, Valhalla, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chia","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, New York Medical College, Valhalla, New 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