Effect of bumetanide on potassium transport and ionic composition of the arterial wall

Abstract

Bumetanide (B) (1 mM) decreased K content of dog carotid arteries (Ka) by 11-15%, K turnover (lambda 2) by 31%, and steady-state K fluxes (JK) by approximately 48%. The drug also reduced intracellular (ic) Cl, H2O, and occasionally ic Na. The half-maximal inhibitory concentration of B on JK was close to 40 microM. However, 10 microM still fully reduced ic K, Cl, and H2O but not ic Na. Replacement of external Cl by sulfate or nitrate mimicked the B effects on JK and reduced its capacity of inhibition by approximately 40 and approximately 80%, respectively. Replacement of Na by choline decreased Ka and JK by 90 and 96%, respectively, and rendered B totally ineffective. B also decreased Cl uptake and content of cultured vascular smooth muscle and ic Cl and H2O of whole arteries. Ouabain (Ou) (1 mM) decreased Ka 90%, accelerated lambda 2 four- to fivefold, and reduced JK 45%. Addition of B or removal of external Na or Cl in the presence of Ou returned lambda 2 to normal levels and reduced the residual JK by approximately 90% but failed to further decrease the Ka. According to these data, B mainly inhibits a coupled KCl passive self exchange plus a smaller active net KCl influx. Ou abolished the active component without affecting the passive self exchange. The presence of Na is necessary for the operation of the KCl-coupled self exchange, and Na gradients may provide the energy for the uphill KCl movements.