Effect of canrenone on the disturbances of cation handling induced by ouabain in macrophages and vascular smooth muscle cells.
Ouabain induced rapid and profound modifications of Na+ and K+ contents in mouse macrophages and cultured vascular smooth muscle cells. In mouse macrophages, we found a one-to-one net Na+ gain and K+ depletion, with a maximal initial rate of 30 to 35 mmol (l X cells X hr)-1 and with an IC50 of about 100 microM. The one-to-one exchange results from at least two additive effects: inhibition of the Na+,K+-pump and stimulation of a furosemide-sensitive, outward Na+,K+-cotransport by the increase in internal Na+ content. The latter effect helps the cell to maintain a normal cell volume in spite of the large changes in internal cation content. In cultured vascular smooth muscle cells from rat aorta, ouabain provoked net Na+ gain and stimulated a quinidine-sensitive, K+-efflux. This likely reflects the opening of Ca+-dependent, K+-channels in response to an increase in cytosolic-free Ca+ content. Canrenone, an antihypertensive drug, has been shown to behave like a partial agonist at the digitalisreceptor site of the Na+,K+-pump. We observed here in mouse macrophages and cultured vascular smooth muscle cells that: canrenone alone (or at low ouabain concentrations) induces slight Na+ gain and K+ depletion; canrenone partially counterbalances the very rapid cell Na+ gain (and K+ depletion) provoked by high ouabain concentrations, and canrenone reverses the secondary effects of ouabain on the Na+,K+-cotransport system and Ca+-dependent, K+-channels. It appears therefore that canrenone may partially reverse the disturbances of cation handling induced by high concentrations of ouabain in macrophages and vascular smooth muscle cells.
D000818:Animals; D001692:Biological Transport; D002192:Canrenone / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D008433:Mathematics; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D011245:Pregnadienes / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D011245:Pregnadienes; D010042:Ouabain; D002192:Canrenone; D005665:Furosemide; D012964:Sodium; D011188:Potassium