AJP - Renal Physiology, Vol 260, Issue 4 536-F548, Copyright © 1991 by American Physiological Society
Aldosterone metabolism in combined isolated perfused rat liver and kidney
M. Egfjord, H. Daugaard and K. Olgaard
Medical Department P, Rigshospitalet, Copenhagen, Denmark.
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.
