Clonidine and noradrenaline fail to inhibit vagal induced bradycardia

Summary

Guinea pig isolated right atria were used to test for inhibitory prejunctional α-adrenoceptors on terminal cardiac vagal varicosities. These receptors have been considered to be involved in reciprocal inhibition of transmitter release.

Electrical field pulses delivered during the atrial refractory period caused biphasic changes in atrial period. An immediate bradycardia was followed by a more gradual tachycardia. An estimation of both parasympathetic and sympathetic transmitter release following a single stimulation was made possible by the tempral separation of the peak brahycardia and tachycardia.

In one set of atria two stimulus-response curves were constructed with a 30 min interval. The sympathetic (tachycardia) stimulus-response curve was stable, but the second parasympathetic (bradycardia) curve was significantly attenuated compared with the first.

In a second set of atria clonidine (1 μM) was added to the bathing solution after the first curve. In these tissues the tachycardia phase of the responses was almost abolished in the second curve. The parasympathetic responses were similar to those in the time control tissues.

In a third set of tissues phentolamine (1 μM) was added after the first curve. This caused a significant increase in the resting period (bradycardia). There was no significant difference between the first and the second curves in these tissues.

In a fourth group of atria propranolol (1 μM) was added after the first curve. This caused a significant attenuation of the sympathetic responses, but the parasympathetic responses were not different from the first curve. A third set of stimuli was applied after half of the tissues were exposed to noradrenaline (1 μM). The third curves were not different from the second curves with or without the presence of noradrenaline.

These experiments suggest that there are no inhibitory prejunctional α-adrenoceptors on the terminal vagal varicosities in the guinea pig right atrium. This finding provides evidence against the hypothesis of reciprocal inhibition of transmitter release.