Inhibition of macula densa-stimulated renin secretion by pharmacological blockade of cyclooxygenase-2

Previous results from our laboratory have shown that in the isolated perfus ed juxtaglomerular apparatus, nonselective inhibitors of cyclooxygenase (CO X) activity prevent the stimulation of renin secretion by a reduction in lu minal NaCl concentration at the macula densa. The present studies were perf ormed to examine which COX isoform is involved in NaCl-dependent renin secr etion. 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 ra te from 4.5 +/- 1.8 to 26.1 +/- 7.4 nGU/min (P < 0.01, n = 19). The presenc e of the COX-1 inhibitor valerylsalicylate (500 mu M) in lumen and bath did not affect the stimulation of renin secretion by a reduction in luminal Na Cl concentration (5 +/- 1.8 nGU/min at high NaCl, and 30.5 +/- 9.4 nGU/min at low NaCl; P < 0.01, n = 8). In contrast, the specific COX-2 inhibitor NS -398 (50 mu M) in lumen and bath abolished the stimulating effect of low lu minal NaCl (12.8 +/- 3.9 nGU/min at high NaCl, and 10.7 +/- 3.1 nGU/min at low NaCl; NS, n = 15). The finding that COX-2 is critically involved in mac ula densa control of renin secretion indicates that the COX-2-expressing ep ithelial cells in the tubuloglomerular contact area are a likely source of prostaglandins participating in the signaling pathway between the macula de nsa and renin-producing granular cells.