LOOP DIURETICS BLOCK CALCIUM CURRENTS IN CARDIAC-CELLS

Loop diuretics are widely used drugs; serving to alleviate congestive heart failure and hypertension [1, 2]. 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 [3]. 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 [1, 4-6]. 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. © 1991.