AFLUID November 46/5

Traynor, Timothy R.,Ann Smart, Josephine P. Briggs, and Jurgen Schnermann. Inhibition of macula densastimulated renin secretion by pharmacological blockade of cyclooxygenase-2. Am. J. Physiol. 277 (Renal Physiol. 46): F706–F710, 1999.—Previous results from our laboratory have shown that in the isolated perfused juxtaglomerular apparatus, nonselective inhibitors of cyclooxygenase (COX) activity prevent the stimulation of renin secretion by a reduction in luminal NaCl concentration at the macula densa. The present studies were performed to examine which COX isoform is involved in NaCl-dependent renin secretion. In the absence of COX inhibitors, a reduction in luminal NaCl (from Na 141/Cl 120 mM to Na 26/Cl 7 mM) caused an increase in renin secretion rate from 4.5 6 1.8 to 26.1 6 7.4 nGU/min (P , 0.01, n 5 19). The presence of the COX-1 inhibitor valerylsalicylate (500 μM) in lumen and bath did not affect the stimulation of renin secretion by a reduction in luminal NaCl concentration (5 6 1.8 nGU/min at high NaCl, and 30.5 6 9.4 nGU/min at low NaCl; P , 0.01, n 5 8). In contrast, the specific COX-2 inhibitor NS-398 (50 μM) in lumen and bath abolished the stimulating effect of low luminal NaCl (12.8 6 3.9 nGU/min at high NaCl, and 10.7 6 3.1 nGU/min at low NaCl; NS, n 5 15). The finding that COX-2 is critically involved in macula densa control of renin secretion indicates that the COX-2-expressing epithelial cells in the tubuloglomerular contact area are a likely source of prostaglandins participating in the signaling pathway between the macula densa and renin-producing granular cells.