Pollock D M, Morsing P
Vascular Biology Center, Medical College of Georgia, Augusta 30912-2500, USA.
J Am Soc Nephrol. 1999 Jan;10 Suppl 11:S116-9.
The current study was conducted to determine the potential influence of ibuprofen on the renal and systemic response to AT1 receptor blockade in conscious rats developing spontaneous hypertension. Experiments used spontaneously hypertensive rats (SHR) during the early developmental phase of hypertension (6 to 7 wk old). Six groups of rats were given the following during a 2-wk treatment protocol: (1) candesartan cilexetil (AT1 receptor antagonist) at 1 mg/kg body wt per d; (2) candesartan cilexetil at 10 mg/kg per d; (3) ibuprofen at 30 mg/kg per d; (4) a combination of candesartan cilexetil at 1 mg/kg per d + ibuprofen; (5) candesartan cilexetil at 10 mg/kg per d + ibuprofen; and (6) untreated (controls). All compounds were added to the drinking water at concentrations adjusted to maintain the desired dosage. In the young untreated SHR, systolic arterial pressure significantly increased from 134+/-4 to 170+/-11 mmHg. Candesartan at 1 mg/kg per d prevented any increase in arterial pressure (131+/-5 mmHg at week 0 versus 131+/-4 mmHg at week 2). At a dose of 10 mg/kg per d, candesartan lowered arterial pressure from 131+/-2 to 91+/-4 mmHg. Ibuprofen treatment alone had no effect on the increase in arterial pressure observed in young SHR over the study period, and had no effect on the changes produced by candesartan at either dose. In the two groups of rats receiving candesartan at 10 mg/kg per d (with and without ibuprofen), a significant increase in urine volume and water intake was observed; urine volume rose from 9.5+/-1.0 to 22.9+/-1.1 ml/d in rats given only candesartan and from 11.5+/-0.7 to 22.0+/-0.6 ml/d in rats given candesartan + ibuprofen. Urine volume and water intake were unchanged in all other groups. These effects on water handling are consistent with previous findings that chronic angiotensin II inhibition inhibits water reabsorption in the kidney. These results demonstrate that nonsteroidal anti-inflammatory drug treatment has no effect on the antihypertensive efficacy and diuretic effects of AT1 receptor blockade in rats developing hypertension.
本研究旨在确定布洛芬对自发性高血压清醒大鼠肾及全身对AT1受体阻断反应的潜在影响。实验选用高血压早期发育阶段（6至7周龄）的自发性高血压大鼠（SHR）。在为期2周的治疗方案中，将大鼠分为六组，分别给予以下处理：（1）坎地沙坦酯（AT1受体拮抗剂），剂量为1毫克/千克体重/天；（2）坎地沙坦酯，剂量为10毫克/千克/天；（3）布洛芬，剂量为30毫克/千克/天；（4）坎地沙坦酯1毫克/千克/天 + 布洛芬；（5）坎地沙坦酯10毫克/千克/天 + 布洛芬；（6）未处理（对照组）。所有化合物均以调整后的浓度添加到饮用水中，以维持所需剂量。在未处理的年轻SHR中，收缩压从134±4显著升高至170±11毫米汞柱。每天1毫克/千克的坎地沙坦可防止动脉压升高（第0周时为131±5毫米汞柱，第2周时为131±4毫米汞柱）。剂量为每天10毫克/千克时，坎地沙坦可使动脉压从131±2降至91±4毫米汞柱。在整个研究期间，单独使用布洛芬对年轻SHR中观察到的动脉压升高没有影响，对两种剂量的坎地沙坦所产生的变化也没有影响。在两组每天接受10毫克/千克坎地沙坦治疗的大鼠（含或不含布洛芬）中，观察到尿量和饮水量显著增加；仅给予坎地沙坦的大鼠尿量从9.5±1.0毫升/天增加到22.9±1.1毫升/天，给予坎地沙坦 + 布洛芬的大鼠尿量从11.5±0.7毫升/天增加到22.0±0.6毫升/天。其他所有组的尿量和饮水量均未改变。这些对水代谢的影响与先前的研究结果一致，即慢性抑制血管紧张素II可抑制肾脏对水的重吸收。这些结果表明，非甾体抗炎药治疗对高血压大鼠中AT1受体阻断的降压疗效和利尿作用没有影响。
