TY - JOUR
T1 - Hepatic extraction of renin
T2 - Quantitation and characterization in the isolated perfused rat liver
AU - Keiser, Joan A.
AU - Romero, Juan C.
AU - Kost, Louis J.
AU - Larusso, Nicholas F.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1987
Y1 - 1987
N2 - Since the liver is thought to be the major organ for the metabolism of renin, the rate‐limiting enzyme in the renin‐angiotensin cascade, we examined the kinetics and regulation of renin extraction by the isolated perfused rat liver. Partially purified, hog kidney renin was continuously infused into isolated rat livers perfused in a nonrecirculating manner with serum‐free medium. Concentrations of renin in the portal and hepatic veins were measured by radioimmunoassay and first‐pass hepatic extraction calculated. In livers from normal rats, steady‐state, first‐pass hepatic extraction of porcine renin ranged from 12.3 ± 0.9 to 25.5 ± 3.9% of the infused dose; at high renin infusion rates, hepatic extraction was saturable. Administration of captopril, a converting enzyme inhibitor, decreased hepatic extraction of renin by approximately 60%; enalaprilat, another converting enzyme inhibitor, had no effect. First‐pass hepatic extraction of renin was also inhibited by the bile acid, taurocholate, in a dose‐dependent manner. However, bilateral nephrectomy, which reduced endogenous plasma renin activity to unmeasurable levels, had no significant effect on hepatic extraction of renin by livers isolated from nephrectomized rats. These results demonstrate directly that the liver extracts renin in a dose‐dependent and saturable manner, although the precise mechanism of uptake remains to be determined.
AB - Since the liver is thought to be the major organ for the metabolism of renin, the rate‐limiting enzyme in the renin‐angiotensin cascade, we examined the kinetics and regulation of renin extraction by the isolated perfused rat liver. Partially purified, hog kidney renin was continuously infused into isolated rat livers perfused in a nonrecirculating manner with serum‐free medium. Concentrations of renin in the portal and hepatic veins were measured by radioimmunoassay and first‐pass hepatic extraction calculated. In livers from normal rats, steady‐state, first‐pass hepatic extraction of porcine renin ranged from 12.3 ± 0.9 to 25.5 ± 3.9% of the infused dose; at high renin infusion rates, hepatic extraction was saturable. Administration of captopril, a converting enzyme inhibitor, decreased hepatic extraction of renin by approximately 60%; enalaprilat, another converting enzyme inhibitor, had no effect. First‐pass hepatic extraction of renin was also inhibited by the bile acid, taurocholate, in a dose‐dependent manner. However, bilateral nephrectomy, which reduced endogenous plasma renin activity to unmeasurable levels, had no significant effect on hepatic extraction of renin by livers isolated from nephrectomized rats. These results demonstrate directly that the liver extracts renin in a dose‐dependent and saturable manner, although the precise mechanism of uptake remains to be determined.
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U2 - 10.1002/hep.1840070613
DO - 10.1002/hep.1840070613
M3 - Article
C2 - 2824314
AN - SCOPUS:0023583001
SN - 0270-9139
VL - 7
SP - 1254
EP - 1261
JO - Hepatology
JF - Hepatology
IS - 6
ER -