Riegger A J
Medizinische Universitätsklinik Würzburg.
Herz. 1991 Apr;16(2):116-23.
Conditions like heart failure that augment the activity of neurohumoral mechanisms i.e. the renin-angiotensin systems, sympathetic nerve activity and vasopressin secretion are commonly associated with a decreased effective blood volume and a reduced renal perfusion. This leads to an increased dependence of renal hemodynamics on endogenous renal prostaglandin synthesis as a vasodilator and natriuretic counter-regulating system. We investigated the role of prostaglandins in renal functional control in an experimental setting of congestive heart failure by chronic inhibition of cyclooxygenase by indomethacin. In chronic moderate heart failure plasma levels of prostaglandin E2 and prostacyclin were unchanged whereas the urinary excretion of prostaglandin E2 was significantly increased, indicating an augmented synthesis within the kidney (Figures 1 to 3). After inhibition of prostaglandin synthesis we observed a profound increase of renal vascular resistance associated with a reduction of effective renal plasma flow and renal blood flow. This was mainly due to a constriction of the vas afferens of the glomerulum. This led to an impairment of renal function indicated by an increase of serum creatinine and blood urea nitrogen associated with a reduction of urinary flow and fluid retention (Figures 4 and 5). We also studied in a randomized, double-blind, placebo-controlled, parallel-group trial in 40 patients with congestive heart failure effects of acetylsalicylic acid (500 mg t.i.d.) on renal functional parameters. In patients with normal sodium intake acetylsalicylic acid reduced urinary prostaglandin E2 concentration by 37% which led to a reduction of daily urinary sodium excretion by 29% in comparison to placebo (Figure 6). These results clearly show the importance of vasodilator prostaglandins in the regulation of kidney function in heart failure where inhibition of cyclooxygenase results in profound deterioration of renal perfusion and kidney function and retention of fluid and sodium.
诸如心力衰竭等增强神经体液机制（即肾素 - 血管紧张素系统、交感神经活动和血管加压素分泌）活性的病症，通常与有效血容量减少和肾灌注降低相关。这导致肾血流动力学对内源性肾前列腺素合成的依赖性增加，肾前列腺素合成作为一种血管舒张和利钠的反调节系统。我们通过吲哚美辛对环氧化酶的慢性抑制，在充血性心力衰竭的实验环境中研究了前列腺素在肾功能控制中的作用。在慢性中度心力衰竭中，前列腺素E2和前列环素的血浆水平未发生变化，而前列腺素E2的尿排泄量显著增加，表明肾脏内合成增加（图1至3）。在抑制前列腺素合成后，我们观察到肾血管阻力显著增加，同时有效肾血浆流量和肾血流量减少。这主要是由于肾小球入球小动脉的收缩。这导致肾功能受损，表现为血清肌酐和血尿素氮增加，同时尿流量减少和液体潴留（图4和5）。我们还在一项随机、双盲、安慰剂对照、平行组试验中，研究了乙酰水杨酸（500毫克，每日三次）对40例充血性心力衰竭患者肾功能参数的影响。在钠摄入正常的患者中，与安慰剂相比，乙酰水杨酸使尿前列腺素E2浓度降低了37%，导致每日尿钠排泄量减少了29%（图6）。这些结果清楚地表明，血管舒张性前列腺素在心力衰竭肾功能调节中具有重要作用，其中环氧化酶的抑制会导致肾灌注和肾功能严重恶化以及液体和钠潴留。
