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Angiotensin II Induces Prostaglandin E2 Production and Oxidative Stress in the Renal Cortex
Author(s) -
Alanazi Wael Abdullah,
Fakhruddin Selim,
Jackson Keith
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1198.6
Subject(s) - angiotensin ii , endocrinology , medicine , chemistry , renal blood flow , renal cortex , prostaglandin e2 , microdialysis , kidney , renal function , oxidative stress , angiotensin ii receptor type 1 , receptor , central nervous system
Angiotensin II (AngII) is a systemic vasoconstrictor and body fluid regulator. Virtually all released AngII binds to AT1 receptors, which stimulates cell signaling pathways in various cell types. In kidneys, AngII enhances arachidonic acid release by increasing the activity of phospholipases enzymes and cyclooxygenase‐2 (COX‐2), leading to an elevation of PGs predominantly prostaglandin E2 (PGE2). Thus, the current study hypothesizes that acute AngII infusion induces the local production of PGE2 and oxidative stress in the renal cortex, which results in renal damage. Male Sprague Dawley rats (200 – 300g) were anesthetized and microdialysis probes were placed in the renal cortex. After a stabilization period, a 4 hour control period was followed by vehicle or AngII (7ng/kg/min, IV) treatment for 4 hours. Blood pressure was elevated significantly during AngII infusion from (109.8 ± 0.085mmHg) to (129.36 ± 0.1mmHg). Urine flow, urinary Na + /K + excretion, glomerular filtration rate, and renal blood flow were decreased in comparison with control. Through renal microdialysis, we found that PGE2 levels were significantly induced by AngII treatment when compared to control. In addition, acute AngII infusion augmented the present oxidative stress in the renal tissues. Superoxide and peroxynitrite levels were evaluated by EPR using CPH and CMH as spin traps. In the current study, we found that local effects of acute AngII infusion stimulate PGE2 and free radical release producing a disruption in normal renal hemodynamic function. In summary, the current study demonstrates a potential mechanism by which acute elevations in AngII promotes hypertension induced end organ kidney damage. Support or Funding Information Saudi Arabian Cultural Mission (SACM), INBRE