Abstract

Transmural electrical stimulation applied at the isolated rabbit sinoatrial node caused a frequency-dependent increase in the atrial rate in the presence of atropine. In response to transmural stimulation, the tension of spiral strips of the rabbit ascending aorta transiently increased. The application of bretylium in concentrations higher than 5 x10^-6 M inhibited the contractile response of aortae to a greater extent than it inhibited the positive chronotropic response of atria. The responses of atria and aortae were potentiated and prolonged by treatment with cocaine (3 x 10^-6 M) and desipramine (2 x 1O^-7 M) . The inhibition of the responses by bretylium was prevented by prior application of cocaine or desipramine and was reversed to the potentiation by cocaine when applied to preparations in which the inhibition had already been established. Treatment with excess Ca⁺⁺, Na⁺ deficiency and ouabain (2 x 10^-7 M) potentiated and prolonged the responses of atria and aortae to transmural stimulation but did not antagonize the inhibitory effect of bretylium. Trends of potentiating the effect of bretylium were observed in atria and aortae exposed to excess Ca⁺⁺ and Na⁺ deficiency. It is therefore concluded that antagonism of bretylium's effects by cocaine and desipramine may not be associated with an inhibition of the membrane transport system but primarily with the mechanism by which breylium is inactivated intraneuronally and/or actively extruded from adrenergic neurons.