Diminished inotropic responsiveness to ouabain in aged rat myocardium.

Abstract

The effect of advanced age on the response to paired pacing and on the relationship between ouabain-induced inotropy and inhibition of (Na + K)-ATPase in hearts from young adult and senescent rats was studied. In isometric trabeculae carneae control values of developed tension (DT) and maximal rate of tension development (dT/dt) and the response to extrasystolic potentiation at prematurity intervals from 400 ms to the mechanical refractory period were not age related. The maximal response occurred at a prematurity interval of 200 ms and was above 200% of control. The inotropic response to ouabain occurred over a concentration range from 2 .times. 10-6-6 .times. 10-5 M. DT and dT/dt in muscles from the young adult group exhibited a greater response than those from the senescent group; e.g., at 6 .times. 10-5 M parameters were approximately 4 times greater in the former group. Ouabain-induced enzyme inhibition, which occurred over the same concentration range as did ouabain-induced changes in mechanical function was not age dependent. Apparently paired pacing but not ouabain results in similar increases in inotropy and therefore similar increases in myoplasmic Ca concentration in young adult and aged rat myocardium. The age-dependent difference in ouabain responsiveness appears to be related to an age-associated alteration in a step other than enzyme inhibition linking ouabain binding to increased myoplasmic Ca levels.