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(Hypertension. 1999;34:1163-1167.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Natriuretic Response to Increased Pressure Is Preserved With COX-2 Inhibitors

Presented in part at the 31st Annual Meeting of the American Society of Nephrology, Philadelphia, Pa, October 25, 1998, and published in abstract form (J Am Soc Neph. 1998; 9:306A).

Jennifer M. Gross; Jennifer E. Dwyer; Franklyn G. Knox

From the Departments of Medicine and Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, Minn.

Correspondence to Franklyn G. Knox, MD, PhD, Departments of Medicine and Physiology and Biophysics, Mayo Clinic and Mayo Foundation, 200 First St SW, Rochester, MN 55905. E-mail knox.franklyn{at}mayo.edu

Abstract—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 (FE_Na) 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 (2.3±0.5 mm Hg, P<0.05) and FE_Na (1.1±0.3%, P<0.05). Likewise, in animals infused with NS-398 or meloxicam, direct renal interstitial volume expansion significantly increased RIHP (1.8±0.6 mm Hg, P<0.05, and 1.7±0.3 mm Hg, P<0.05) and FE_Na (1.5±0.4%, P<0.05, and 1.1±0.3%, P<0.05), respectively. In contrast, infusion of piroxicam significantly blunted the natriuretic response to direct renal interstitial volume expansion (FE_Na 0.3±0.2%), even though RIHP was increased (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.

Key Words: sodium • prostaglandins • kidney

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