Modulation of noradrenaline release through presynaptic alpha 2-adrenoceptors in congestive heart failure.
Stimulation of presynaptic alpha 2-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 alpha 2-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 [delta NAph]). Plasma noradrenaline concentration at rest, NAph, and delta NAph 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 delta Naph (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 alpha 2-adrenoceptors in patients with congestive heart failure, and this buffer serves to protect organs such as the heart from excess sympathetic stimulation.
Minatoguchi
S
S
Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
Ito
H
H
Ishimura
K
K
Watanabe
H
H
Imai
Y
Y
Koshiji
M
M
Asano
K
K
Hirakawa
S
S
Fujiwara
H
H
D000368:Aged; D004837:Epinephrine / Q000097:blood; D005246:Feedback / Q000187:drug effects; D006333:Heart Failure / Q000097:blood* / Q000145:classification / Q000188:drug therapy; D006801:Humans; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D010646:Phentolamine / Q000008:administration & dosage; D011224:Prazosin / Q000008:administration & dosage; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D018341:Receptors, Adrenergic, alpha-2; D017661:Receptors, Presynaptic; D005996:Nitroglycerin; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine