Gross J M, Dwyer J E, Knox F G
Departments of Medicine and Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Hypertension. 1999 Nov;34(5):1163-7. doi: 10.1161/01.hyp.34.5.1163.
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 (Delta2.3+/-0.5 mm Hg, P<0. 05) and FE(Na) (Delta1.1+/-0.3%, P<0.05). Likewise, in animals infused with NS-398 or meloxicam, direct renal interstitial volume expansion significantly increased RIHP (Delta1.8+/-0.6 mm Hg, P<0.05, and Delta1.7+/-0.3 mm Hg, P<0.05) and FE(Na) (Delta1.5+/-0.4%, P<0. 05, and Delta1.1+/-0.3%, P<0.05), respectively. In contrast, infusion of piroxicam significantly blunted the natriuretic response to direct renal interstitial volume expansion (DeltaFE(Na) 0.3+/-0. 2%), even though RIHP was increased (Delta1.9+/-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.
通过直接扩张肾间质容积来升高肾间质静水压（RIHP）可增加钠排泄。这种利钠反应会因环氧化酶（COX）酶的非特异性抑制而减弱。本研究检验了以下假设：在直接扩张肾间质容积期间，对升高的RIHP的利钠反应依赖于COX - 1而非COX - 2。在对照大鼠（n = 7）、输注COX - 1抑制剂吡罗昔康的大鼠（n = 6，1.5 mg/kg）以及输注COX - 2抑制剂NS - 398的大鼠（n = 5，1.5 mg/kg）和输注美洛昔康的大鼠（n = 6，0.3 mg/kg）中，在直接扩张肾间质容积前后测量RIHP和钠分数排泄（FE(Na)）。在对照动物中，直接扩张肾间质容积显著增加了RIHP（Δ2.3±0.5 mmHg，P < 0.05）和FE(Na)（Δ1.1±0.3%，P < 0.05）。同样，在输注NS - 398或美洛昔康的动物中，直接扩张肾间质容积分别显著增加了RIHP（Δ1.8±0.6 mmHg，P < 0.05，以及Δ1.7±0.3 mmHg，P < 0.05）和FE(Na)（Δ1.5±0.4%，P < 0.05，以及Δ1.1±0.3%，P < 0.05）。相比之下，输注吡罗昔康显著减弱了对直接扩张肾间质容积的利钠反应（ΔFE(Na) 0.3±0.2%），尽管RIHP升高了（Δ1.9±0.6 mmHg，P < 0.05）。输注吡罗昔康而非NS - 398或美洛昔康减弱了对升高的肾间质静水压的利钠反应，这表明在抑制COX - 2期间，对升高血压的利钠反应可能得以保留。
