Fricker A F, Nussberger J, Meilenbrock S, Brunner H R, Burnier M
Division of Hypertension and Vascular Medicine, University Hospital, Lausanne, Switzerland.
Kidney Int. 1998 Dec;54(6):2089-97. doi: 10.1046/j.1523-1755.1998.00220.x.
Non-steroidal anti-inflammatory drugs are known to promote sodium retention and to blunt the blood pressure lowering effects of several classes of antihypertensive agents including beta-blockers, diuretics and angiotensin converting enzyme (ACE) inhibitors. The purpose of the present study was to investigate the acute and sustained effects of indomethacin on the renal response to the angiotensin II receptor antagonist valsartan and to the ACE inhibitor enalapril.
Twenty normotensive subjects maintained on fixed sodium intake (100 mmol sodium/day) were randomized to receive for one week: valsartan 80 mg o.d., enalapril 20 mg o.d., valsartan 80 mg o.d. + indomethacin 50 mg bid and enalapril 20 mg o.d. + indomethacin 50 mg bid. This single-blind study was designed as a parallel (valsartan vs. enalapril) and cross-over trial (valsartan or enalapril vs. valsartan + indomethacin or enalapril + indomethacin). Renal hemodynamics and urinary electrolyte excretion were measured for six hours after the first and seventh administration of each treatment regimen.
The results show that valsartan and enalapril have comparable renal effects characterized by no change in glomerular filtration rate and significant increases in renal plasma flow and sodium excretion. The valsartan- and enalapril-induced renal vasodilation is not significantly blunted by indomethacin. However, indomethacin similarly abolishes the natriuresis induced by the angiotensin II antagonist and the ACE inhibitor.
This observation suggests that although angiotensin receptor antagonists do not affect prostaglandin metabolism, the administration of a non-steroidal anti-inflammatory drug blunts the natriuretic response to angiotensin receptor blockade.
已知非甾体抗炎药可促进钠潴留，并减弱包括β受体阻滞剂、利尿剂和血管紧张素转换酶（ACE）抑制剂在内的几类抗高血压药物的降压作用。本研究的目的是调查吲哚美辛对血管紧张素II受体拮抗剂缬沙坦和ACE抑制剂依那普利的肾脏反应的急性和持续影响。
20名血压正常且钠摄入量固定（100 mmol钠/天）的受试者被随机分组，接受为期一周的治疗：缬沙坦80 mg每日一次、依那普利20 mg每日一次、缬沙坦80 mg每日一次 + 吲哚美辛50 mg每日两次以及依那普利20 mg每日一次 + 吲哚美辛50 mg每日两次。这项单盲研究设计为平行试验（缬沙坦与依那普利对比）和交叉试验（缬沙坦或依那普利与缬沙坦 + 吲哚美辛或依那普利 + 吲哚美辛对比）。在每种治疗方案首次和第七次给药后6小时测量肾脏血流动力学和尿电解质排泄。
结果显示，缬沙坦和依那普利具有相似的肾脏效应，其特征为肾小球滤过率无变化，肾血浆流量和钠排泄显著增加。吲哚美辛并未显著减弱缬沙坦和依那普利诱导的肾血管舒张。然而，吲哚美辛同样消除了血管紧张素II拮抗剂和ACE抑制剂诱导的利钠作用。
该观察结果表明，尽管血管紧张素受体拮抗剂不影响前列腺素代谢，但非甾体抗炎药的给药会减弱对血管紧张素受体阻断的利钠反应。
