Natriuretic response to increased pressure is preserved with COX-2 inhibitors

Elevation of renal interstitial hydrostatic pressure (RIHP) by direct renal interstitial volume expansion increases sodium excretion. This natriuretic response is blunted by the nonspecific inhibition of the cyclooxygenase (COX) enzymes. The present study tested the hypothesis that the natriuretic response to increased RIHP during direct renal interstitial volume expansion is dependent on COX-1 but not COX-2. RIHP and fractional excretion of sodium (FENa) were measured before and after direct renal interstitial volume expansion in control rats (n=7), rats infused with the COX-1 inhibitor piroxicam (n=6, 1.5 mg/kg), and rats infused with the COX-2 inhibitors NS-398 (n=5, 1.5 mg/kg) and meloxicam (n=6, 0.3 mg/kg). In control animals, direct renal interstitial volume expansion significantly increased RIHP (Delta 2.3+/-0.5 mm Hg, P<0.05) and FENa (Delta 1.1+/-0.3%, P<0.05). Likewise, in animals infused with NS-398 or meloxicam, direct renal interstitial volume expansion significantly increased RIHP (Delta 1.8+/-0.6 mmHg, P<0.05, and Delta 1.7+/-0.3 mm Hg, P<0.05) and FENa (Delta 1.5+/-0.4%, P<0.05, and Delta 1.1+/-0.3%, P<0.05), respectively. In contrast, infusion of piroxicam significantly blunted the natriuretic response to direct renal interstitial volume expansion (Delta FENa 0.3+/-0.2%), even though RIHP was increased (Delta 1.9+/-0.6 mm Hg, P<0.05). Infusion of piroxicam but not NS-398 or meloxicam blunted the natriuretic response to increased renal interstitial hydrostatic pressure, suggesting that the natriuretic response to increased blood pressure may be preserved during inhibition of COX-2.