大鼠肝肾联合离体灌注中的醛固酮代谢

Egfjord M, Daugaard H, Olgaard K

Medical Department P, Rigshospitalet, Copenhagen, Denmark.

Am J Physiol. 1991 Apr;260(4 Pt 2):F536-48. doi: 10.1152/ajprenal.1991.260.4.F536.

The metabolism of aldosterone (Aldo) at 4 nM was studied by radioimmunoassay and by high-performance liquid chromatography in isolated perfused liver (IPL), isolated perfused kidney (IPK), and combined isolated perfused liver and kidney (CIPLK) of male Wistar rats. Effect of D[4-(14)C]aldosterone (D [4-(14)C]Aldo) on the function of IPK of intact and adrenalectomized (ADX) rats was also studied. Aldo clearance in the liver was most important, 16.3 +/- 1.7 ml/min. In IPK, the total clearance of Aldo was 0.27 +/- 0.36 ml/min (39% of the glomerular filtration rate) (GFR). Fractional excretion (FE) of Aldo was 16 +/- 8%. Metabolic clearance of Aldo was (0.21 +/- 0.23 ml/min), 78% of total renal clearance. In CIPLK, the kidney inhibited hepatic clearance of Aldo by 23% when compared with IPL (P less than 0.05). Hepatic Aldo metabolites were predominantly eliminated by biliary excretion of polar metabolites. Several hepatic polar metabolites and tetrahydroaldosterone (THA) accumulated in perfusate and were excreted in the urine in a similar pattern. After hydrolysis of the polar metabolites, some coeluated with THA and dihydroaldosterone (DHA), whereas other metabolites remained more polar than Aldo. Without addition of Aldo, in IPK of ADX rats FENa was higher (P less than 0.01), and FEK was lower (P less than 0.01), resulting in three- to fourfold higher urinary Na-K ratio (P less than 0.01) when compared with IPK and CIPLK of intact rats. In IPK of ADX rats with Aldo in perfusate, only FEK was restored. Addition of Aldo to IPK of intact rats had no effect. However, only in CIPLK, addition of Aldo resulted in an increasing kaliuresis in three subsequent periods of 30 min (0.56-0.95, P less than 0.01). Thus the hepatic metabolites of Aldo could in part mediate the kaliuretic effect of Aldo.

采用放射免疫分析法和高效液相色谱法，对雄性Wistar大鼠的离体灌注肝脏（IPL）、离体灌注肾脏（IPK）以及联合离体灌注肝脏和肾脏（CIPLK）中4 nM醛固酮（Aldo）的代谢进行了研究。还研究了D[4-(14)C]醛固酮（D [4-(14)C]Aldo）对完整大鼠和肾上腺切除（ADX）大鼠的IPK功能的影响。肝脏中Aldo的清除最为重要，为16.3±1.7 ml/min。在IPK中，Aldo的总清除率为0.27±0.36 ml/min（占肾小球滤过率（GFR）的39%）。Aldo的分数排泄（FE）为16±8%。Aldo的代谢清除率为（0.21±0.23 ml/min），占肾脏总清除率的78%。在CIPLK中，与IPL相比，肾脏使肝脏对Aldo的清除率降低了23%（P<0.05）。肝脏Aldo代谢产物主要通过极性代谢产物的胆汁排泄而消除。几种肝脏极性代谢产物和四氢醛固酮（THA）在灌注液中积累，并以类似模式随尿液排出。极性代谢产物水解后，一些与THA和二氢醛固酮（DHA）共洗脱，而其他代谢产物的极性仍比Aldo大。在未添加Aldo的情况下，ADX大鼠的IPK中FENa较高（P<0.01），FEK较低（P<0.01），与完整大鼠的IPK和CIPLK相比，尿钠钾比高3至4倍（P<0.01）。在灌注液中添加Aldo的ADX大鼠的IPK中，仅FEK恢复。向完整大鼠的IPK中添加Aldo没有效果。然而，仅在CIPLK中，添加Aldo导致在随后三个30分钟的时间段内尿钾排泄增加（0.56 - 0.95，P<0.01）。因此，Aldo的肝脏代谢产物可部分介导Aldo的利钾作用。