MPS 18-05 MINERALOCORTICOID RECEPTOR RESPONSIBLE FOR SALT INDUCED COX2 EXPRESSION IN RENAL MEDULLA. (September 2016)

• Record Type: Journal Article
• Authors: Reheman, Latapati; Hirohama, Daigoro; Koid, SuangSunag; Wang, Conghui; Mori, Fumiko; Yeerbolati, Alimila; Liu, Beibei; Yatomi, Yutaka; Fujita, Toshiro; Shimosawa, Tatsuo
• Is Part Of: Journal of hypertension. Volume 34:(2016) Supplement 1
• Publication Date: 2016-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000501091.21439.97
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Cyclooxygenase (COX), a rate-limiting enzyme in the prostaglandin (PG) biosynthesis pathway, exists in two major isoforms: constitutive COX-1 and inducible COX-2. High-salt loading increases the expression of COX-2 in the renal medulla, however the mechanism of this phenomenon remains poorly understood. In salt-sensitive hypertension, the mineralocorticoid receptor (MR) is activated and ROS levels increased. Furthermore, previous study showed that aldosterone stimulation increases COX2 expression in macula densa cells. In the present study we evaluated the role of MR and ROS on high-salt-induced COX2 expression and PGE2 levels. Design and Method: 3-week-old Sprague-Dawley (SD) rats were subjected to left uninephrectomy and subsequently divided into the following groups: (i) normal-salt (NS; 0.3% NaCl) and (ii) high-salt (HS; 8% NaCl) diet for 1, 2 and 4 weeks; (iii) HS diet plus the antioxidant superoxide dismutase mimetic 4-hydroxy-2, 2, 6, 6-tetramethyl-piperidine-N-oxyl, Tempol (0.6 mmol.kg −1 .day −1 in drinking water) for 4 weeks; (iv) HS diet plus treatment with the MR blocker eplerenone (Ep; 100 mg kg −1 .day −1 in chow) for 4 weeks. Body weight, blood pressure, urinary PGE2 levels and renal function were evaluated. Results: In current study I used young age of SD rat with UNX and high salt loading which was proper model for salt sensitive hypertension experiment. 1 week after HS loading, COX2 mRNA and protein levels, and urinary PGE2 levels were higher than that of the NS group. 2 and 4weeks after HS loading COX2 mRNA and protein levels decreased, although urinary PGE2 levels increased significantly compared with NS group. Hypertension and kidney dysfunction were also observed at 2week and 4week□after HS loading. 4 weeks of HS treatment with tempol or Eplerenone reversed COX2 mRNA and protein expression, and PGE2 levels when compared to the HS group. Conclusions: Taken together, the MR and ROS may explain the increases in COX2 expression in the renal medulla in high-salt loading Figure. No caption available.