{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:00:51Z","timestamp":1760148051486,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["#HL-65289","#HL-72920","HL-092026"],"award-info":[{"award-number":["#HL-65289","#HL-72920","HL-092026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>In Dahl salt-sensitive (SS) rats, impaired vascular relaxation can be restored by: (1) minipump infusion of a low (sub-pressor) dose of angiotensin II (ANG II) to restore physiological levels of plasma ANG II, (2) inhibition of 20-HETE production, and (3) introgression of a normally functioning renin allele from the Brown Norway rat (SS-13BN consomic rat). Unlike SS rats, SS-13BN rats have normal levels of ANG II on a normal-salt diet and suppressed ANG II on a high-salt (HS) diet. This study tested whether chronically low ANG II levels in SS rats upregulate cytochrome P450-4A (CYP4A) increasing the production of the vasoconstrictor 20-HETE. Although salt-induced suppression of ANG II levels increased reactive oxygen species (ROS) in basilar arteries from SS-13BN rats in previous studies, this study showed no change in vascular 20-HETE levels in response to ANGII suppression. CYP4A inhibition significantly reduced vascular ROS levels and restored endothelium-dependent relaxation in response to acetylcholine in the middle cerebral artery (MCA) of SS rats and HS-fed SS-13BN rats. These data demonstrate that both the renin\u2013angiotensin system and the CYP4A\/20-HETE pathway play a direct role in the vascular dysfunction of the Dahl SS rat but are independent of each other, even though they may both contribute to vascular dysfunction through ROS production.<\/jats:p>","DOI":"10.3390\/antiox12040783","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T03:07:57Z","timestamp":1679540877000},"page":"783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Chronically Suppressed Plasma Angiotensin II on Regulation of the CYP4A\/20-HETE Pathway in the Dahl Salt-Sensitive Rat"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2898-7719","authenticated-orcid":false,"given":"Kathleen","family":"Lukaszewicz","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, Marquette University, Milwaukee, WI 53233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9219-7845","authenticated-orcid":false,"given":"John","family":"Falck","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical School, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Lombard","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1001\/jama.280.13.1168","article-title":"Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. 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