[Effect of amiloride and its derivative dichlorobenzamil on guinea pig atria: interaction with other inotropic mechanisms].

Abstract

The inotropic and chronotropic effects of Amiloride (AMI) and Dichloro-benzamil Amiloride (DBC-AMI) were studied on the guinea pig isolated atria, also, the interaction between these drugs and Beta-methyl-Digoxin (BM-DIGO), epinephrine and low extracellular potassium (1 mM). AMI (10(-3) M) has a negative chronotropic and positive inotropic effects, not dependent on the autonomic system. DCB-AMI has a bimodal effect on the contractile force: increases it at low concentrations but causes a decrease at concentrations higher than 10(-6) M. The effect of AMI on the sinus frequency is unchanged by BM-DIGO. AMI (10(-3) M) decreases the inotropic effect of BM-DIGO and increases the toxic concentration of this drug on isolated tissues. The dose-response curve to epinephrine was not changed by AMI. Similar results were obtained using DCB-AMI (2 x 10(-7) M). The positive inotropic effect obtained by low extracellular potassium (1 mM) was not altered by AMI. The activity of the Mg(++)-dependent, Na+/K+ ATPase measured in the microsomal fraction obtained from guinea pig heart was diminished (10%) by AMI (10(-3) M). The drug did not affect the inhibition of the enzyme induced by ouabain. In conclusion, our experiments show multiple effects of AMI and DCB-AMI on the guinea pig heart. The inhibition of the Na+/Ca++ exchange explains them only partially. A slow channel blocking effect appears fundamental to interpret our results.