Loop diuretics block calcium currents in cardiac cells.

Abstract

Loop diuretics are widely used drugs; serving to alleviate congestive heart failure and hypertension. Their mechanism of action is considered to be an inhibition of sodium retention in the kidneys, by a block of the Na/K/Cl cotransporter. The ensuing natriuresis and diuresis reduces blood pressure and alleviates congestive heart failure. Several earlier reports suggested direct cardiovascular effects, partly preceding the onset of diuresis. In the present study, evidence is presented for a direct action of two loop diuretic agents, bumetanide and furosemide, on cardiac L-type calcium currents in rabbit ventricular and atrial myocytes. This current is reversibly reduced by micromolar concentrations of these drugs. The onset of this effect can be observed within 1-2s, which could indicate a direct action on the calcium channel, independent of secondary effects subsequent to inhibition of the cotransporter. Thus, part of the therapeutic effects of the loop diuretics may be achieved through a direct reduction of cardiac output.