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National Institute of Diabetes, and Digestive and Kidney Diseases, Bethesda, Maryland 20892
Experiments were performed in mice to investigate whether
cyclooxygenase-2 (COX-2) in epithelial cells near the tubulovascular contact point (macula densa and TAL cells) may regulate renin gene
expression in juxtaglomerular granular cells. Renin activity, afferent
arteriolar granularity, and renin mRNA were determined in wild-type
mice and in COX-2-knockout mice on control and low-NaCl diets. Renin
activity in microdissected glomeruli assessed as angiotensin I
formation in the presence of excess substrate and afferent arteriolar
granularity determined by direct visualization and immunostaining were
significantly reduced in COX-2 
/ compared with wild-type animals.
Similarly, renal cortical mRNA levels were lower in COX-2 / than in
wild-type mice. Maintaining mice on a low-salt diet for 14 days induced
an increase in renin mRNA, afferent arteriolar granularity, and renin
activity in wild-type mice. In contrast, renin mRNA and renin
granularity did not significantly increase in low-salt-treated COX-2
/ mice, whereas the increase in juxtaglomerular renin enzyme
activity was markedly attenuated, but not fully blocked. In additional
experiments we found that COX-2 mRNA was increased in angiotensin type
1A receptor-knockout mice compared with wild-type mice. We conclude
that COX-2 in the tubulovascular contact region is a critical
determinant of renin synthesis in granular cells under resting
conditions and that it participates in the stimulation of renin
expression caused by a low-NaCl intake.
renin activity; prostaglandins; macula densa; juxtaglomerular apparatus cyclooxygenase-2
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