Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II.
Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II.
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DOI：
10.1172/jci14752
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发表时间：
2002-07
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影响因子：
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通讯作者：
Z. Qi;C. Hao;R. Langenbach;R. Breyer;R. Redha;J. Morrow;M. Breyer
中科院分区：
文献类型：
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作者：
Z. Qi;C. Hao;R. Langenbach;R. Breyer;R. Redha;J. Morrow;M. Breyer
环加氧酶抑制（COX 抑制）非甾体抗炎药 (NSAID) 的治疗使用通常会因高血压和水肿等肾脏副作用而变得复杂。目前的研究旨在阐明 COX1 和 COX2 在调节血压和肾功能中的作用。 COX2 抑制剂或基因敲除可显着增强血管紧张素 II (Ang II) 的升压作用。出乎意料的是，在短暂增加后，Ang II 的升压作用被 COX1 缺陷（抑制剂或敲除）所消除。 Ang II 输注还减少了 COX2 缺陷动物的髓质血流量，但在对照或 COX1 缺陷动物中没有减少，这表明肾髓质中合成了 COX2 依赖性血管扩张剂。与此一致的是，Ang II 未能刺激 COX2 缺陷动物肾髓质前列腺素 E(2) 和前列腺素 I(2) 的产生。 Ang II输注通常会促进尿钠排泄和利尿，但COX2缺乏会阻碍这种作用。因此，COX1和COX2对全身血压和肾功能发挥相反的作用。 COX2抑制剂减少肾髓质血流量，减少尿流量，增强Ang II的升压作用。相反，COX1 抑制会削弱 Ang II 的升压作用。这些结果表明，COX1 和 COX2 的活性在功能上是拮抗的，而不是具有类似的心血管作用。
Therapeutic use of cyclooxygenase-inhibiting (COX-inhibiting) nonsteroidal antiinflammatory drugs (NSAIDs) is often complicated by renal side effects including hypertension and edema. The present studies were undertaken to elucidate the roles of COX1 and COX2 in regulating blood pressure and renal function. COX2 inhibitors or gene knockout dramatically augment the pressor effect of angiotensin II (Ang II). Unexpectedly, after a brief increase, the pressor effect of Ang II was abolished by COX1 deficiency (either inhibitor or knockout). Ang II infusion also reduced medullary blood flow in COX2-deficient but not in control or COX1-deficient animals, suggesting synthesis of COX2-dependent vasodilators in the renal medulla. Consistent with this, Ang II failed to stimulate renal medullary prostaglandin E(2) and prostaglandin I(2) production in COX2-deficient animals. Ang II infusion normally promotes natriuresis and diuresis, but COX2 deficiency blocked this effect. Thus, COX1 and COX2 exert opposite effects on systemic blood pressure and renal function. COX2 inhibitors reduce renal medullary blood flow, decrease urine flow, and enhance the pressor effect of Ang II. In contrast, the pressor effect of Ang II is blunted by COX1 inhibition. These results suggest that, rather than having similar cardiovascular effects, the activities of COX1 and COX2 are functionally antagonistic.