Expression of cyclooxygenase-2 in the juxtaglomerular apparatus of angiotensinogen gene-knockout mice.
OBJECTIVE
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%.


CONCLUSIONS
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.
Hashimoto
Tatsuo
T
Division of Cellular Pathobiology, Department of Pathology, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
Kihara
Minoru
M
Sato
Keiko
K
Matsushita
Kei
K
Tanimoto
Keiji
K
Toya
Yoshiyuki
Y
Fukamizu
Akiyoshi
A
Umemura
Satoshi
S
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D001794:Blood Pressure; D003404:Creatinine / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007191:Indazoles / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000201:enzymology*; D007672:Kidney Cortex / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007191:Indazoles; D017673:Sodium Chloride, Dietary; D000808:Angiotensinogen; D003404:Creatinine; D052248:Nitric Oxide Synthase Type I; D051546:Cyclooxygenase 2; C080122:7-nitroindazole