Expression of Cyclooxygenase-2 in the Juxtaglomerular Apparatus of Angiotensinogen Gene-Knockout Mice

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Abstract
Aims: The present study was designed to examine the role of the renin-angiotensin system in the regulation of macula densa cyclooxygenase-2 (COX-2) during altered dietary salt intake. Methods: We investigated COX-2 expression in the macula densa of angiotensinogen gene-knockout (Atg–/–) mice. COX-2 expression in the renal cortex was determined by real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Results: The renal cortical expression of COX-2 mRNA increased 24.7 times in Atg–/– mice compared with Atg+/+ mice. When Atg--/– mice were fed a high-salt diet (4% NaCl) for 10 days, the levels of COX-2 expression were markedly suppressed. The macula densa COX-2 immunoreactivity was correlated with the mRNA expression. The selective inhibition of neuronal isoform of nitric oxide synthase (N-NOS) activity by 7-nitroindazole significantly reduced the levels of COX-2 mRNA in Atg–/– mice by 54.1%. Conclusion: These results suggest that (1) COX-2 activity in the macula densa can be regulated by salt intake through a mechanism independent of the renin-angiotensin system, and (2) COX-2 expression is functionally linked to renal cortical N-NOS activity in Atg–/– mice.