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

Abstract

—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 ...