Suppression of Plasma Renin Activity by Indomethacin in Man
Suppression of Plasma Renin Activity by Indomethacin in Man
复制标题
吲哚美辛对人血浆肾素活性的抑制
作者：
Ürgen C. FrÖlich;J. Hollifield;J. C. Dormois;Brigitte L. FrOlich;Hanns örg Seyberth;A. Michelakis;J. Oates
吲哚美辛或安慰剂对醛固酮、血浆肾素活性（PRA）、钠排泄和尿前列腺素（PC）水平的影响在5名钠平衡为100 mEq的高血压受试者中进行了研究，这些受试者过去曾经历过恶性高血压伴肾素-醛固酮关系紊乱。吲哚美辛显著降低醛固酮水平43%，PRA 58%，24小时钠排泄量49%，尿PC排泄量（肾PC合成的指标）67%。血管紧张素输注增加醛固酮与吲哚美辛治疗前后相同。同样，在150 mEq钠平衡的正常受试者中，吲哚美辛使PRA降低47%;钠排泄下降33%，尿前列腺素E（PGE）排泄下降55%。静脉注射呋塞米10分钟后PRA的急性升高被吲哚美辛完全消除。5例原发性高血压患者根据其对口服呋塞米的反应被归类为正常肾素高血压患者。吲哚美辛预处理导致呋塞米后PRA降低60%，其中3例受试者现在属于低肾素类别。体外研究表明，吲哚美辛对肾素-肾素底物相互作用没有影响。因此，吲哚美辛降低PRA伴随着肾PC合成活性的降低。吲哚美辛是否通过肾内、PG相关机制或继发性钠潴留抑制肾素释放进行了讨论。
The effect of indomethacin or placebo on aldosterone, plasma renin activity (PRA), sodium excretion, and urinary prostaglandin (PC) levels was investigated in five hypertensive subjects in 100 mEq sodium balance who had experienced malignant hypertension with a disturbance of their renin-aldosterooe relationship in the past. Indomethacin significantly lowered aldosterone levels by 43%, PRA by 58%, 24-hour sodium excretion by 49%, and urinary PC excretion, an indicator of renal PC synthesis, by 67%. Angiotensin infusion increased aldosterone to the same level before and after treatment with indomethacin. Similarly, in normal subjects in 150 mEq sodium balance, indomethacin lowered PRA by 47%; sodium excretion fell by 33%, and urinary prostaglandin E (PGE) excretion, by 55%. The acute elevation in PRA 10 minutes after intravenous furosemide was completely abolished by indomethacin. Five subjects with essential hypertension were classified as normal renin hypertensives according to their response to orally administered furosemide. Indomethacin pretreatment resulted in 60% reduction of PRA following furosemide, and three of these subjects now fell into the low renin category. Studies in vitro demonstrated that indomethacin has no effect on the renin-renin substrate interaction. Thus, indomethacin lowers PRA concomitantly with a reduction in renal PC synthetise activity. Whether indomethacin inhibits renin release by an intrarenal, PG-related mechanism or secondarily via sodium retention is discussed.