Renocortical expression of renin and of cyclooxygenase-2 in response to angiotensin 11 AT(1) receptor blockade is closely coordinated but not causally linked

Based on recent evidence that renin gene and cyclooxygenase-2 (COX-2) expre ssion in the rat kidney cortex increase in parallel under a variety of cond itions, this study aimed to characterize the causal linkage between COX-2 a nd renin expression. Therefore, we semi-quantitated renocortical renin and COX-2 gene expression when the renin-angiotensin system (RAS) was inhibited by the angiotensin II (Ang II) AT1 receptor antagonist candesartan (15 mg/ kg per day) and when COX-2 activity was blocked by celecoxib (20 mg/kg twic e a day) in three rat strains (Sprague-Dawley, WKY and SHR) at ages of 5, 9 and 15 weeks. We observed that candesartan increased renin mRNA in all rat s at all ages, the amplitude of stimulation being inversely related to age. Candesartan increased COX-2 mRNA in all three strains at 5 weeks, and in S ID and WKY rats also at 9 weeks. In 9-week-old SUR and in 15-week-old rats of all three strains candesartan did not influence COX-2 mRNA levels. For a ll rat strains, strain-specific strong linear correlations existed between renocortical COX-2 and renin mRNA levels, both with and without candesartan treatment. The additional feeding of candesartan-treated rats with celecox ib did not change renin mRNA or COX-2 mRNA levels, whilst the renal excreti on of sodium and renal cortical prostaglandin E-2 concentration decreased b y 26% and 60%, respectively. In summary, these findings, obtained when the renin system was activated by AT(1) receptor blockade, indicate that Ang II is not required to stimulate COX-2 expression and that COX-2 activity is n ot required to stimulate renin expression. However, the renocortical expres sion of renin and of COX-2 appear to be highly coordinated under basal cond itions and during inhibition of RAS, suggesting the existence of a common d enominator for renin and COX-2 expression that remains to be elucidated.