INFLUENCE OF SOME INHIBITORS AND IONS ON THE POSITIVE INOTROPIC ACTION OF EPINEPHRINE, TYRAMINE AND CALCIUM

¹ Department of Biochemistry, St. Louis University School of Medicine, St. Louis, Missouri

On the electrically stimulated rat ventricle strip, propranolol, fluorodinitrobenzene and sodium fluoride neither altered the control contractile force nor affected the positive inotropic action of calcium, but did markedly reduce the action of both epinephrine and tyramine. Increasing the concentration of calcium in the bathing medium from 0.625 to 2.50 mM increased the contractile force of the ventricle muscle but decreased its response to epinephrine, tyramine or additional calcium. The contractile force of the ventricle muscle was increased by decreasing the extracellular sodium from 140 to 35 mM, but the positive inotropic action of epinephrine, tyramine or calcium was reduced. Increasing potassium from 2.9 to 11.6 mM in the medium depressed the contractile force, but the effect of epinephrine, tyramine or calcium was increased. Changing the concentration of magnesium from 0.6 to 2.4 mM did not alter appreciably the control contractile force of the ventricle muscle, or the action of calcium, epinephrine and tyramine. Increasing pH of the medium from 6.6 to 8.4 modified neither the control contractile force nor the action of tyramine and calcium, whereas the positive inotropic action of epinephrine was augmented by a shift of pH from 6.6 to 7.8. These results indicate that the degree of positive isotropic action of epinephrine, tyramine or calcium is dependent upon the extracellular milieu of sodium, potassium and calcium. It is suggested that sympathomimetic agents produce positive inotropic action by increasing intracellular concentration of calcium available for the contractile process, and that certain steps involved in this manifestation are energy-dependent.