Kramp R A, Caron N, Genard J, Lejeune C, Gulbis E, Herman A
Service de Physiologie et Pharmacologie, Faculté de Médecine, Université de Mons-Hainaut, Mons, Belgium.
Eur J Pharmacol. 1997 Jul 9;330(2-3):165-76. doi: 10.1016/s0014-2999(97)00178-7.
Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n = 6), but mean arterial pressure was significantly decreased (by 15 mmHg) with sulindac (n = 12). In the 5 mg/kg b.w. sulindac group (n = 7), renal blood flow progressively and significantly increased from 7.88 +/- 0.36 to 8.98 +/- 0.58 ml/min, except during concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n = 7). The pressure limits for efficient and no renal blood flow autoregulation remained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac group (n = 5), renal blood flow did not change but autoregulatory pressure limits were lowered by 10 mmHg 2 h after treatment (P < 0.025). Also, Na+ retention was marked. Prostanoid excretion in urine was significantly reduced with either dose but basal plasma renin activity was not (about 8 ng/ml per h; n = 15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n = 21), it was decreased from 11.5 +/- 1.2 to 7.4 +/- 0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P < 0.05; n = 6). In conclusion, differential effects of sulindac on renal hemodynamics, Na+ excretion and plasma renin activity were demonstrated. Renal hemodynamic changes could be related in part to the cytochrome P-450 arachidonic acid pathway.
在麻醉大鼠中，通过电磁血管周围血流传感器研究肾脏血流动力学，这些大鼠经静脉注射溶媒、5或10毫克/千克体重的舒林酸。注射溶媒的大鼠（n = 6）未出现血流动力学变化，但注射舒林酸的大鼠（n = 12）平均动脉压显著降低（降低15 mmHg）。在5毫克/千克体重舒林酸组（n = 7）中，肾血流量从7.88±0.36逐渐显著增加至8.98±0.58毫升/分钟，除了同时每小时肾内输注3毫克/千克体重丙磺舒的大鼠（n = 7）。有效和无肾血流自动调节的压力极限保持不变（分别约为100和80 mmHg）。在10毫克/千克体重舒林酸组（n = 5）中，肾血流量未改变，但治疗2小时后自动调节压力极限降低了10 mmHg（P < 0.025）。此外，钠潴留明显。两种剂量的舒林酸均使尿中前列腺素排泄显著减少，但基础血浆肾素活性未受影响（约8纳克/毫升·小时；n = 15）。当肾灌注压降低后血浆肾素活性增强时（n = 21），仅10毫克/千克体重舒林酸使其从11.5±1.2降至7.4±0.2纳克/毫升·小时（P < 0.05；n = 6）。总之，证明了舒林酸对肾脏血流动力学、钠排泄和血浆肾素活性有不同影响。肾脏血流动力学变化可能部分与细胞色素P - 450花生四烯酸途径有关。
