Modulation of noradrenaline release through presynaptic α2-adrenoceptors in congestive heart failure

Stimulation of presynaptic α2-adrenoceptors inhibits the release of noradrenaline from sympathetic nerve endings; however, the extent to which it operates in patients with congestive heart failure is still unknown. To investigate the degree of negative feedback to the release of noradrenaline via presynaptic α2-adrenoceptors at sympathetic nerve endings, we measured plasma noradrenaline levels before and after the injection of phentolamine (i.e., plasma noradrenaline concentration at rest, plasma noradrenaline concentration after phentolamine injection [NAph], and the phentolamine-induced increase in plasma noradrenaline [ΔNAph]). Plasma noradrenaline concentration at rest, NAph, and ΔNAph increased in a stepwise manner from New York Heart Association class I to class III. A positive correlation was found between the plasma noradrenaline at rest and ΔNAph (n = 123, R = 0.697, p < 0.001). These results suggest that the enhanced release of plasma noradrenaline is substantially buffered by the mechanism of noradrenaline release-inhibitory presynaptic α2-adrenoceptors in patients with congestive heart failure, and this buffer serves to protect organs such as the heart from excess sympathetic stimulation.