Prejunctional modulation of noradrenaline release by alpha 2-adrenoceptors: physiological and pharmacological implications in the cardiovascular system.

The modulation of noradrenaline release from sympathetic nerves by presynaptic alpha 2-adrenoceptors has now been demonstrated in a variety of tissues. The heart is a particularly useful organ in which to study the modulation of noradrenaline release both in vivo and in vitro for two reasons: (a) the postsynaptic adrenoceptors are of the beta-subtype; and (b) the ease with which the sympathetic nerve supply can be isolated and stimulated electrically. Blood vessels however have been difficult to study directly due to the fact that they possess postsynaptic alpha-adrenoceptors and to the lack of a good in vivo model of a discrete vascular bed. Using both in vivo and in vitro preparations, it was demonstrated that the sympathetic innervation of the heart and blood vessels possesses a functional negative feedback system modulating noradrenaline release mediated via alpha 2-adrenoceptors. The effect of this system depends upon the frequency of nerve stimulation and the total number of stimuli. This article covers some of the more recent contributions to the understanding of the presynaptic modulation of noradrenaline release that have been made by the study of the peripheral cardiovascular system.