Romero J C, Strong C G
Circ Res. 1977 Jan;40(1):35-41. doi: 10.1161/01.res.40.1.35.
Indomethacin inhibits the synthesis of prostaglandin and the release of renin. These effects were studied in normal rabbits and rabbits with two-kidney Goldblatt hypertension (2KGH) and one-kidney Goldblatt hypertension (1KGH) by giving daily intravenous injections of indomethacin (3mg/kg after two initial doses of 9 mg/kg), and in appropriate control rabbits given diluent phosphate buffer without indomethacin. In normal rabbits, indomethacin significantly decreased immunoreactive plasma prostaglandin E-like substance (IPGE) and plasma renin activity (PRA). Indomethacin did not change plasma creatinine (PCr) or mean blood pressure but it decreased renal blood flow (RBF) and glomerular filtration rate (GFR). In 2KGH rabbits, responses depended on the level of renal function and, to a lesser extent, on the level of PRA. In six of10 2KGH rabbits in which hypertension developed without significant changes in PRA, IPGE, PCr, RBF, and GFR, indomethacin produced changes similar to those seen in normals. In the other four rabbits, development of 2KGH was accompanied by increased PRA, increased IPGE, and decreased RBF and GFR, and indomethacin produced renal failure, oliguria, malignant hypertension, and death within 5 days. In 1KGH rabbits, indomethacin decreased IPGE, PRA, and renal function but increased mean blood pressure. These observations suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.
吲哚美辛可抑制前列腺素的合成及肾素的释放。通过每日静脉注射吲哚美辛（首剂9mg/kg，之后3mg/kg），在正常兔以及双肾型Goldblatt高血压（2KGH）兔和单肾型Goldblatt高血压（1KGH）兔中研究了这些效应，并设置给予不含吲哚美辛的稀释磷酸盐缓冲液的适当对照兔。在正常兔中，吲哚美辛显著降低免疫反应性血浆前列腺素E样物质（IPGE）及血浆肾素活性（PRA）。吲哚美辛未改变血浆肌酐（PCr）或平均血压，但降低了肾血流量（RBF）和肾小球滤过率（GFR）。在2KGH兔中，反应取决于肾功能水平，在较小程度上也取决于PRA水平。在10只2KGH兔中有6只，其高血压发生时PRA、IPGE、PCr、RBF和GFR无显著变化，吲哚美辛产生的变化与正常兔相似。在另外4只兔中，2KGH的发生伴随着PRA升高、IPGE升高以及RBF和GFR降低，吲哚美辛在5天内导致肾衰竭、少尿、恶性高血压及死亡。在1KGH兔中，吲哚美辛降低了IPGE、PRA及肾功能，但升高了平均血压。这些观察结果提示，前列腺素在肾血管性高血压中对肾功能发挥保护作用。
