Izhar Munavvar, Alausa Tunji, Folker Amy, Hung Elena, Bakris George L
Rush Medical Center, 1700 W. Van Buren St, Suite 470, Chicago, IL 60612, USA.
Hypertension. 2004 Mar;43(3):573-7. doi: 10.1161/01.HYP.0000115921.55353.e0. Epub 2004 Jan 26.
Cyclo-oxygenase (COX) inhibitors attenuate the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors and reduce kidney function. The study tests the hypothesis that these two classes of drugs have similar effects on glomerular filtration rate (GFR) and 24-hour blood pressure. The primary endpoint was change in 24-hour systolic blood pressure. Using a randomized crossover design, 25 black and Hispanic hypertensive participants (mean age 58+/-3 years) with osteoarthritis were studied. All participants received an ACE inhibitor at baseline. Once systolic blood pressure was <140 mm Hg, either celecoxib 200 mg/d or diclofenac 75 mg twice daily for 4 weeks was started. After measurements were obtained, all participants underwent a 2-week washout period and crossed over to the other drug for 4 weeks. A significant difference in mean 24-hour systolic blood pressure was noted between groups at 4 weeks (+4.1+/-1.1 mm Hg diclofenac versus +0.6+/-0.6 mm Hg celecoxib; P=0.01). However, because celecoxib has duration of action shorter than 24 hours, we compared ambulatory values at celecoxib trough and peak activities. At peak, no difference in systolic blood pressure was noted between agents (+3.6+/-0.04 mm Hg diclofenac versus +4.2+/-1.9 mm Hg celecoxib; P=0.67). GFR was also differentially affected at 24 hours (-9.9+/-2.4 mL/min diclofenac versus -0.4+/-1.2 mL/min celecoxib; P=0.01). We conclude that diclofenac and celecoxib increase systolic blood pressure at peak levels; however, these agents differ in their 24-hour effects. Differences observed in blood pressure response between COX inhibitors may not be related in their sensitivity but rather their dosing frequency.
环氧化酶（COX）抑制剂会减弱血管紧张素转换酶（ACE）抑制剂的降压作用并降低肾功能。本研究检验了这样一个假设，即这两类药物对肾小球滤过率（GFR）和24小时血压有相似的影响。主要终点是24小时收缩压的变化。采用随机交叉设计，对25名患有骨关节炎的黑人和西班牙裔高血压参与者（平均年龄58±3岁）进行了研究。所有参与者在基线时接受一种ACE抑制剂治疗。一旦收缩压<140 mmHg，就开始给予塞来昔布200 mg/d或双氯芬酸75 mg每日两次，持续4周。在获得测量值后，所有参与者都经历了为期2周的洗脱期，然后交叉使用另一种药物4周。4周时，两组之间的平均24小时收缩压存在显著差异（双氯芬酸组为+4.1±1.1 mmHg，塞来昔布组为+0.6±0.6 mmHg；P = 0.01）。然而，由于塞来昔布的作用持续时间短于24小时，我们比较了塞来昔布谷值和峰值活性时的动态血压值。在峰值时，两种药物的收缩压没有差异（双氯芬酸组为+3.6±0.04 mmHg，塞来昔布组为+4.2±1.9 mmHg；P = 0.67）。24小时时GFR也受到不同程度的影响（双氯芬酸组为-9.9±2.4 mL/min，塞来昔布组为-0.4±1.2 mL/min；P = 0.01）。我们得出结论，双氯芬酸和塞来昔布在峰值水平时会升高收缩压；然而，这些药物在24小时的作用有所不同。COX抑制剂之间观察到的血压反应差异可能与其敏感性无关，而与其给药频率有关。
