Diminished Inotropic Responsiveness to Ouabain in Aged Rat Myocardium

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We studied the effect of advanced age on the response to paired pacing and on the relationship between ouabain-induced inotropy and inhibition of (Na + K)-ATPas in hearts from young adult and senescent rats. In isometric trabeculae carneae, control values of developed tension (DT) and maximal rate of tension development (dT/dt) were not age-related. There was no age-related difference in the response to extrasystolic potentiation at prematurity intervals from 400 msec to the mechanical refractory period. The maximal response occurred at a prematurity interval of 200 msec and was above 200% of control. The inotropic response to ouabain occurred over a concentration range from 2 ∼ 10~6 to 6 ∼ 10′s 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 ∼ 10′s M both parameters were approximately four times greater in the former group. There was no age-dependent difference in ouabain-induced enzyme inhibition, which occurred over the same concentration range as did ouabain-induced alterations in mechanical function. These data indicate that paired pacing, but not ouabain, results in similar increases in inotropy and therefore similar increases in myoplasmic calcium 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 calcium levels. Circ Res 44: 517-523, 1979

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