title: The effect of potassium canrenoate (Aldactone) on the norepinephrine metabolism and potassium ionic currents of the heart.
abstract: Under experimental conditions, potassium canrenoate causes a significant increase in [3H]norepinephrine (NE) uptake by the heart, although the NE content remains unchanged. The increased NE uptake and unchanged NE content indicate an augmented NE turnover caused by the drug. In saluretic-pretreated animals, the intracellular hypopotassemia can be restored by Aldactone. This effect can be explained by the inhibition of the outward potassium current. When we simulated the pathophysiological conditions of the acute phase of myocardial infarction by using a K+-rich superfusate to partially depolarize the myocardial cells, slow action potentials were elicited by NE in isolated papillary muscles. Our microelectrode experiments revealed that Aldactone, by its blocking effect on the potassium conductance, increases the duration of the slow action potentials and decreases the threshold NE concentration required to elicit the slow responses. However, in clinical conditions with a higher level of circulating catecholamine and/or hyperpotassemia, the administration of the drug has a considerable risk of provoking arrhythmias.
mesh_terms: D000818:Animals; D002191:Canrenoic Acid / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D009115:Muridae; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011245:Pregnadienes / Q000494:pharmacology*; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D011245:Pregnadienes; D013148:Spironolactone; D002191:Canrenoic Acid; D010293:Pargyline; D011188:Potassium; D009638:Norepinephrine