Influence of angiotensin converting enzyme inhibitor (captopril) on kidney epithelial cells in vitro: studies on potassium (86Rb) influx and cellular proliferation.
The effects of captopril on potassium influx and cellular proliferation in a dog kidney epithelial cell line (Madin-Darby canine kidney cells, MDCK) were studied. Na+K(+)-ATPase activity and the loop diuretic sensitive Na/K/2Cl- cotransport were measured using 86Rb as tracer substance. Cells were incubated with various concentrations of captopril (1-10 mmol/l). The furosemide sensitive Na/K/2Cl- cotransport was significantly decreased from 1 mmol/l onwards. Na+/K(+)-ATPase activity was lowered only when high amounts (10 mmol/l) of the drug were used. Cell proliferation was measured via [3H]thymidine incorporation. After incubation with 1 mmol/l captopril proliferation was strongly decreased (greater than 50%). Higher amounts (5-10 mmol/l) did not further suppress cell proliferation. The data suggest that natriuresis following ACE inhibition in vivo does not involve a direct effect of captopril on Na+K(+)-ATPase. However, the effect on cell proliferation may be of clinical relevance in respect to a possible mitogenic effect of angiotensin II.
Bauer
H
H
Institut für Zoologie, Universität Salzburg, Austria.
Lametschwandtner
A
A
Steiner
M
M
Bauer
H C
HC
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D012414:Rubidium Radioisotopes; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D002352:Carrier Proteins; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D028021:Sodium-Potassium-Chloride Symporters; D005665:Furosemide; D002216:Captopril; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium