Renal and cardiovascular effects of selective cyclooxygenase-2 inhibitors.
Renal and cardiovascular effects of selective cyclooxygenase-2 inhibitors.
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DOI：
10.1053/ajkd.2001.29203
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发表时间：
2001-12
期刊：
影响因子：
--
通讯作者：
R. Komers;S. Anderson;Murray Epstein
中科院分区：
文献类型：
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作者：
R. Komers;S. Anderson;Murray Epstein
选择性抑制环氧合酶-2（考克斯-2）被认为是一种新型的抗炎和镇痛治疗方法，与传统的非甾体抗炎药（NSAID）相比，其胃肠道副作用减少。尽管被认为是炎症和其他刺激的诱导酶，但考克斯-2在肾脏中组成性表达。本文主要综述了考克斯-2在肾脏和心血管（CV）中的生理和病理生理学特征，以及选择性考克斯-2抑制剂治疗肾脏和CV方面的作用。临床和实验研究均表明，考克斯-2抑制剂的肾脏和CV效应与NSAID相似。这些影响包括钠、钾和水潴留，肾功能下降，以及血压（BP）和水肿轻度至中度升高。在血容量和/或钠耗竭的患者中，这些有害作用被放大。伴随使用考克斯-2抑制剂可能会使接受抗高血压药物治疗的高血压患者的血压控制不稳定。与可能构成考克斯-2抑制剂不良作用靶点的正常肾脏相反，最近的实验研究显示，在几种肾损伤模型中，如残肾、肾血管性高血压和糖尿病，肾考克斯-2表达增加，并暗示考克斯-2参与肾衰竭的进展。这表明，考克斯-2抑制剂可能赋予不同的肾脏疾病的肾保护作用。这些有趣的配方必须在适当设计的前瞻性临床试验中进一步描述。
Selective inhibition of cyclooxygenase-2 (COX-2) was proposed as a novel anti-inflammatory and analgesic treatment with a reduced profile of gastrointestinal side effects compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs). Although perceived as an inducible enzyme by inflammatory and other stimuli, COX-2 is constitutively expressed in the kidney. In this review, we focus on renal and cardiovascular (CV) physiological and pathophysiological characteristics of COX-2 and renal and CV aspects of treatment with selective COX-2 inhibitors. Both clinical and experimental studies have shown that renal and CV effects of COX-2 inhibitors are similar to those of NSAIDs. These effects include sodium, potassium, and water retention and decreases in renal function, as well as mild to modest increases in blood pressure (BP) and edema. These deleterious effects are amplified in patients with volume and/or sodium depletion. The concomitant administration of COX-2 inhibitors may destabilize BP control in hypertensive patients treated with antihypertensive agents. In contrast to the normal kidney, which could constitute a target for adverse actions of COX-2 inhibitors, recent experimental studies showed increased renal COX-2 expression in several models of renal injury, such as the remnant kidney, renovascular hypertension, and diabetes, and implicated COX-2 in the progression of renal failure. This suggests that COX-2 inhibitors may confer a renoprotective effect in diverse renal disorders. These intriguing formulations must be delineated further in appropriately designed prospective clinical trials.