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• W2152625019 abstract "Rationale : Cyclooxygenase (COX)-derived prostanoids (PGs) are involved in blood pressure homeostasis. Both traditional nonsteroidal antiinflammatory drugs (NSAIDs) that inhibit COX-1 and COX-2 and NSAIDs designed to be selective for inhibition of COX-2 cause sodium retention and elevate blood pressure. Objective : To elucidate the role of COX-2 in blood pressure homeostasis using COX-1>COX-2 mice, in which the COX-1 expression is controlled by COX-2 regulatory elements. Methods and Results : COX-1>COX-2 mice developed systolic hypertension relative to wild types (WTs) on a high-salt diet (HSD); this was attenuated by a PGI 2 receptor agonist. HSD increased expression of COX-2 in WT mice and of COX-1 in COX-1>COX-2 mice in the inner renal medulla. The HSD augmented in all strains urinary prostanoid metabolite excretion, with the exception of the major PGI 2 metabolite that was suppressed on regular chow and unaltered by the HSD in both mutants. Furthermore, inner renal medullary expression of the receptor for PGI 2 , but not for other prostanoids, was depressed by HSD in WT and even more so in both mutant strains. Increasing osmolarity augmented expression of COX-2 in WT renal medullary interstitial cells and again the increase in formation of PGI 2 observed in WTs was suppressed in cells derived from both mutants. Intramedullary infusion of the PGI 2 receptor agonist increased urine volume and sodium excretion in mice. Conclusions : These studies suggest that dysregulated expression of the COX-2 dependent, PGI 2 biosynthesis/response pathway in the renal inner renal medulla undermines the homeostatic response to a HSD. Inhibition of this pathway may contribute directly to the hypertensive response to NSAIDs." @default.
• W2152625019 created "2016-06-24" @default.
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• W2152625019 date "2010-02-05" @default.
• W2152625019 modified "2023-10-15" @default.
• W2152625019 title "Cyclooxygenase-2–Dependent Prostacyclin Formation and Blood Pressure Homeostasis" @default.
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• W2152625019 doi "https://doi.org/10.1161/circresaha.109.204529" @default.
• W2152625019 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2818801" @default.
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