Abstract

Pretreatment of rabbits with reserpine (1.0 mg/kg i.v.) significantly attenuated the positive inotropic response of electrically driven isolated left atria to a nontoxic concentration of ouabain (8.3 x 10^-7 M) as measured by both per cent and absolute change in force. However, the absolute maximum contraction force (in grams) developed by the reserpinized atria was not significantly different from that seen in the normal atria. Reserpine pretreatment (5.0 mg/kg i.v.) did not prevent the toxic effects of ouabain (3.35 x l0^-6 M).

Chronic (3.0 mg/kg i.p. for 3 days) or acute reserpinization did not affect oxygen consumption of isolated left atria. In vitro reserpinization (1.0 and 10.0 γg/ml) also failed to affect atrial O₂ consumption compared to controls.

Reserpine pretreatment, either in vivo or in vitro did not modify the normal stimulatory effect of ouabain (2.8 x 10^-6 M) on atrial O₂ consumption. In addition, dichloroisoproterenol (DCI) in a concentration reported to block the positive inotropic effects of ouabain on the cat papillary muscle failed to modify the usual ouabain-induced augmentation of atrial O₂ consumption.

The data presented here and elsewhere are generally compatible with the view that the modification of the contractile responses to nontoxic concentrations of ouabain in appropriately reserpinized muscle is due in part to the absence or unavailability of endogenous catecholamines required for the production of ouabain-induced augmentation of contraction. However, other changes caused by reserpinization cannot be excluded as factors possibly contributing to the altered ouabain effects. Our data are not consonant with time hypothesis timat an altered oxidative metabolism resulting from reserpinization is involved in the attenuation of the contraction responses to nontoxic concentrations of ouabain in rabbit atrial tissue.