Chronic cyclooxygenase-2 inhibition blunts low sodium-stimulated renin without changing renal haemodynamics

Background Cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenas e, is found in the macula densa of the renal cortex and is upregulated by d ietary sodium restriction. Because of this discrete cortical localization, we hypothesized that COX-2 plays a role in the chronic stimulation of renin via the macula densa pathway. Methods We examined the effect of the selective COX-2 inhibitor NS 398 in m ale Sprague-Dawley rats. Results A low sodium diet (0.02% NaCl) for 14 days elevated plasma-renin ac tivity (PRA) nine-fold, from 6.1 +/- 2.0 to 54.9 +/- 6.5 ng angiotensin I ( Ang I)/ml per h (P < 0.0001). Selective COX-2 inhibition with NS 398 had no effect on PRA in animals on normal sodium (5.1 +/- 1.3 ng Ang I/ml per h), but decreased PRA by 41% in sodium-restricted rats, to 33.3 +/- 3.6 ng Ang 1/ml per h (P < 0.05). Chronic treatment with NS 398 did not decrease rena l renin content (31.8 +/- 1.8 versus 33.5 +/- 2.6 ng Ang I/ mg per h, with NS 398 versus controls), nor did it influence systemic blood pressure or re nal haemodynamics. Neither urinary sodium excretion nor prostaglandin (PG)E -2 excretion was altered in rats given NS 398. Chronic treatment with the n on-selective COX inhibitor indomethacin during sodium restriction over 5 da ys reduced PRA by 35%, from 29.36 +/- 4.81, to 19.13 +/- 2.88 ng Ang 1/ml p er h (P < 0.05). Indomethacin had no effect on blood pressure or renal bloo d flow but reduced urinary PGE(2) excretion by 70%. Conclusions One component of the chronic stimulation of PRA by dietary sodi um restriction via the macula densa pathway appears to involve the inductio n of COX-2. J Hypertens 2000, 18:1107-1113 (C) Lippincott Williams & Wilkin s.