ISSN:
1432-1912
Keywords:
Angiotensin converting enzyme inhibitor
;
SA-446
;
Probenecid
;
Renal clearance of SA-446
;
Organic anion
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The renal excretory mechanism of an orally active inhibitor of angiotensin converting enzyme (SA-446) was examined in anesthetized dogs. Parenteral administration of this compound resulted in production of constant levels of about 2 mg/l in the plasma (PSA) and the urine concentration was 726±200 mg/l, a level significantly higher than that in the plasma. Renal clearance of SA-446 (CSA) was 2.24±0.34 ml/g·min and was significantly higher than GFR. The clearance ratio (CSA/GFR) of over 1.0 was indicative of a net tubular secretion. Administration of probenecid resulted in a significant rise in PSA and in a significant decrease in urinary excretion but with no change in the plasma protein binding ratio. CSA decreased significantly from 2.24±0.34 to 0.71±0.14 ml/g·min. The inhibotory action of SA-446 (0.02 mg/kg, i.v.) on the pressor response to angiotensin I disappeared at about 50 min, this action being maintained for about 2 h in the probenecid pretreated dog. Since probenecid is a competitive inhibitor of organic anion secretory transport, our results show the net tubular secretion of SA-446, via organic anion transport systems. Prolongation of the action of SA-446, as induced by probenecid may be due to the increase of plasma concentration, by the inhibition of tubular secretion.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00504381
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