Inhibition of the Renin-Angiotensin System Upregulates Cyclooxygenase-2 Expression in the Macula Densa

The expression of cyclooxygenase 2 (COX-2) in the late thick ascending limb, including the macula densa, is found to be upregulated in an activated renin-angiotensin system. How this upregulation is managed is not yet known. We therefore considered the possibility that the stimulation of COX-2 expre...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 1999-09, Vol.34 (3), p.503-507
Main Authors: Wolf, Konrad, Castrop, Hayo, Hartner, Andrea, Goppelt-Strübe, Margarete, Hilgers, Karl F, Kurtz, Armin
Format: Article
Language:English
Subjects:
Angiotensin II - metabolism
Animals
Biological and medical sciences
Cyclooxygenase 1
Cyclooxygenase 2
Endocrine kidney. Renin-angiotensin-aldosterone system
Fundamental and applied biological sciences. Psychology
Isoenzymes - biosynthesis
Isoenzymes - genetics
Kidney Cortex - metabolism
Male
Membrane Proteins
Prostaglandin-Endoperoxide Synthases - biosynthesis
Prostaglandin-Endoperoxide Synthases - genetics
Prostaglandins - metabolism
Rats
Rats, Sprague-Dawley
Renin - metabolism
Renin-Angiotensin System - drug effects
Renin-Angiotensin System - physiology
RNA, Messenger - biosynthesis
Up-Regulation
Vertebrates: endocrinology
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Summary:The expression of cyclooxygenase 2 (COX-2) in the late thick ascending limb, including the macula densa, is found to be upregulated in an activated renin-angiotensin system. How this upregulation is managed is not yet known. We therefore considered the possibility that the stimulation of COX-2 expression is triggered by the activation of the renin-angiotensin system. For this purpose, we treated male Sprague-Dawley rats with the angiotensin I-converting enzyme inhibitor ramipril (10 mg/kg per day), the angiotensin II type 1 (AT1) receptor blocker losartan (30 mg/kg per day), and the angiotensin II type 2 (AT2) receptor blocker PD123319 (6 mg/kg per day) for 4 days. We determined the expression of COX-2 mRNA and protein in the renal cortex. We found that ramipril and the AT1 receptor blocker losartan increased COX-2 mRNA and COX-2 immunoreactivity in the macula densa ≈4-fold, whereas the AT2 blocker PD123319 showed no effect. A low-salt diet (0.02% wt/wt) stimulated COX-2 expression in the kidney cortex
ISSN:0194-911X
1524-4563
DOI:10.1161/01.hyp.34.3.503