Cholesterol affects flow-stimulated cyclooxygenase-2 expression and prostanoid secretion in the cortical collecting duct

American Journal of Physiology. Renal Physiology
Yu LiuRajeev Rohatgi

Abstract

Essential hypertension (eHTN) is associated with hypercholesterolemia, but how cholesterol contributes to eHTN is unknown. Recent evidence demonstrates that short-term dietary cholesterol ingestion induces epithelial Na channel (ENaC)-dependent Na absorption with a subsequent rise in blood pressure (BP), implicating cholesterol in salt-sensitive HTN. Prostaglandin E2 (PGE2), an autocrine/paracrine molecule, is induced by flow in endothelia to vasodilate the vasculature and inhibit ENaC-dependent Na absorption in the renal collecting duct (CD), which reduce BP. We hypothesize that cholesterol suppresses flow-mediated cyclooxygenase-2 (COX-2) expression and PGE2 release in the CD, which, in turn, affects Na absorption. Cortical CDs (CCDs) were microperfused at 0, 1, and 5 nl·min(-1)·mm(-1), and PGE2 release was measured. Secreted PGE2 was similar between no- and low-flow (151 ± 28 vs. 121 ± 48 pg·ml(-1)·mm(-1)) CCDs, but PGE2 was greatest from high-flow (578 ± 146 pg·ml(-1)·mm(-1); P < 0.05) CCDs. Next, mice were fed either a 0 or 1% cholesterol diet, injected with saline to generate high urine flow rates, and CCDs were microdissected for PGE2 secretion. CCDs isolated from cholesterol-fed mice secreted less PGE2 and had a lower P...Continue Reading

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Citations

Jan 22, 2017·Prostaglandins & Other Lipid Mediators·Mukut SharmaTarak Srivastava
Aug 1, 2019·American Journal of Physiology. Renal Physiology·Robert L RepettiRajeev Rohatgi
Sep 8, 2017·American Journal of Physiology. Renal Physiology·Tarak SrivastavaMukut Sharma
Feb 27, 2021·Frontiers in Physiology·Robert RepettiRajeev Rohatgi
Jun 22, 2021·Antioxidants & Redox Signaling·Minchun JiangLi Wang

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