Renin expression in COX-2-knockout mice on normal or low-salt diets

Experiments were performed in mice to investigate whether cyclooxygenase-2 (COX-2) in epithelial cells near the tubulovascular contact point (macula d ensa and TAL cells) may regulate renin gene expression in juxtaglomerular g ranular cells. Renin activity, afferent arteriolar granularity, and renin m RNA 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 a rteriolar granularity determined by direct visualization and immunostaining were significantly reduced in COX-2 -/- compared with wild-type animals. S imilarly, renal cortical mRNA levels were lower in COX-2 -/- than in wild-t ype mice. Maintaining mice on a low-salt diet for 14 days induced an increa se in renin mRNA, afferent arteriolar granularity, and renin activity in wi ld-type mice. In contrast, renin mRNA and renin granularity did not signifi cantly increase in low-salt-treated COX-2 -/- mice, whereas the increase in juxtaglomerular renin enzyme activity was markedly attenuated, but not ful ly blocked. In additional experiments we found that COX-2 mRNA was increase d in angiotensin type 1A receptor-knockout mice compared with wild-type mic e. We conclude that COX-2 in the tubulovascular contact region is a critica l 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.