Captopril inhibits sodium and water transport in the toad skin, a model of the distal nephron.
Captopril (SQ 14225), an orally active angiotensin I-converting enzyme inhibitor (CEI), increases natriuresis and diuresis in man and experimental animals in vivo, as well as in the isolated perfused rat kidney, raising the possibility of a direct renal action of the drug. We tested this hypothesis by studying its effects in the isolated toad skin, a model of the distal nephron devoid of vascular and nervous influences. When added to the dermal bath, captopril caused a reversible, concentration-related decrease in short-circuit current (SCC), a measure of active transepithelial Na transport. Keeping the toads in 0.1 M NaCl for 4 or more days increased sensitivity to the drug, which then inhibited SCC maximally (49 +/- 12% at 3.4 X 10(-3) M, P less than 0.01, n = 10), suggesting its effect might be modulated by endogenous mineralocorticoid activity. Captopril also inhibited the increase in SCC and in osmotic water permeability caused by neurohypophyseal peptides (NHP). The increases in SCC by non-peptidic agents (nystatin, a polyene antibiotic, or norepinephrine, an adrenergic agonist) were not altered, ruling out a generalized toxic effect, or any significant inhibition of the Na pump by captopril. The apparently specific effect of the drug on the permeability responses to NHP seems to be exerted proximally to the apical border, since the response of the latter to other agents was preserved. The present data suggest SH groups may be involved, since other CEI lacking such groups (teprotide and MK-422) do not produce such effects. These observations support the notion that a direct tubular effect may be involved in the increased diuresis and natriuresis observed after administration of captopril.
Orce
G G
GG
Castillo
G A
GA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002022:Bufo arenarum; D002216:Captopril / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D015773:Enalaprilat; D005260:Female; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009399:Nephrons / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009997:Osmotic Pressure; D011392:Proline / Q000031:analogs & derivatives*; D012867:Skin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013722:Teprotide / Q000494:pharmacology; D014867:Water / Q000378:metabolism*
D004151:Dipeptides; D009419:Nerve Tissue Proteins; D014867:Water; D011392:Proline; D002216:Captopril; D012964:Sodium; D013722:Teprotide; D015773:Enalaprilat