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Renal Medullary Interstitial COX-2 (Cyclooxygenase-2) Is Essential in Preventing Salt-Sensitive Hypertension and Maintaining Renal Inner Medulla/Papilla Structural Integrity
- Source :
- Hypertension. 72:1172-1179
- Publication Year :
- 2018
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2018.
-
Abstract
- COX (cyclooxygenase)-derived prostaglandins regulate renal hemodynamics and salt and water homeostasis. Inhibition of COX activity causes blood pressure elevation. In addition, chronic analgesic abuse can induce renal injury, including papillary necrosis. COX-2 is highly expressed in the kidney papilla in renal medullary interstitial cells (RMICs). However, its role in blood pressure and papillary integrity in vivo has not been definitively studied. In mice with selective, inducible RMIC COX-2 deletion, a high-salt diet led to an increase in blood pressure that peaked at 4 to 5 weeks and was associated with increased papillary expression of AQP2 (aquaporin 2) and ENac (epithelial sodium channel) and decreased expression of cystic fibrosis transmembrane conductance regulator. With continued high-salt feeding, the mice with RMIC COX-2 deletion had progressive decreases in blood pressure from its peak. After return to a normal-salt diet for 3 weeks, blood pressure remained low and was associated with a persistent urinary concentrating defect. Within 2 weeks of institution of a high-salt diet, increased apoptotic RMICs and collecting duct cells could be detected in papillae with RMIC deletion of COX-2, and by 9 weeks of high salt, there was a striking loss of the papillae. Therefore, RMIC COX-2 expression plays a crucial role in renal handling water and sodium homeostasis, preventing salt-sensitive hypertension and maintaining structural integrity of papilla.
- Subjects :
- 0301 basic medicine
Epithelial sodium channel
medicine.medical_specialty
Urinary system
Apoptosis
Blood Pressure
Mice, Transgenic
030204 cardiovascular system & hematology
Article
Mice
03 medical and health sciences
0302 clinical medicine
Internal medicine
Internal Medicine
medicine
Animals
Epithelial Sodium Channels
Kidney Medulla
Kidney
Aquaporin 2
business.industry
Major duodenal papilla
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Blood pressure
Cyclooxygenase 2
Renal papilla
Hypertension
business
Homeostasis
Subjects
Details
- ISSN :
- 15244563 and 0194911X
- Volume :
- 72
- Database :
- OpenAIRE
- Journal :
- Hypertension
- Accession number :
- edsair.doi.dedup.....2cc190fefb7896d5b2d507724f1f095a