K. Oe et al., Modulation of norepinephrine release by ATP-dependent K+-channel activators and inhibitors in guinea-pig and human isolated right atrium, CARDIO RES, 43(1), 1999, pp. 125-134
Citations number
44
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objective: The aim of this study was to show, whether ATP sensitive K+ chan
nels (K-ATP channels), are involved in the modulation of norepinephrine (NE
) release from the sympathetic nerves innervating the guinea-pig and human
right atrium. Methods: The resting and stimulation-evoked release of [H-3]n
orepinephrine ([H-3]NE) was measured from the isolated guinea-pig and human
right atrium and the effect of activators and inhibitors of ATP sensitive
K+ channels was studied. Results: Cromakalim (30-300 mu M), a K-ATP channel
-agonist decreased concentration-dependently the stimulation-evoked release
of NE from the guinea-pig atrium, an effect, antagonized by glibenclamide,
a K-ATP channel-antagonist (30 mu M). Diazoxide (30-300 mu M), another act
ivator of the K-ATP channels reduced the resting release of NE, and also at
tenuated the evoked release at a single concentration (100 mu M), and this
latter action was also counteracted by glibenclamide (30 mu M). Pinacidil,
increased dose-dependently the resting and stimulation-evoked release of NE
in a glibenclamide-sensitive manner and reversed the inhibitory effect of
cromakalim (100 mu M), suggesting that it acts as an antagonist. Glibenclam
ide (30-300 mu M), by itself enhanced the stimulation-evoked release of [H-
3]NE, and also increased the resting release of NE. On the other hand, 5-hy
droxydecanoate, an ischemia-selective inhibitor of cardiac K-ATP channels d
id not change NE release. Adenosine, (30-300 mu M), an A(1)-receptor agonis
t, clonidine (3 mu M), an alpha(2)-adrenoceptor agonist and oxotremorine, a
muscarinic receptor agonist (30 mu M) all reduced the evoked release of [H
-3]NE, but these effects were not modified by glibenclamide (300 mu M), ind
icating that neuronal adenosine (A(1)), adrenergic (alpha(2)) and muscarini
c (M-3) receptors do not act on K-ATP channels, in the human right atrium,
cromakalim, and diazoxide did not affect significantly the release of [H-3]
NE. However, glibenclamide (30-300 mu M) and pinacidil (30-300 mu M) enhanc
ed dose-dependently the evoked-release of NE, and pinacidil also augmented
the resting release. Conclusions: Our results indicate that sympathetic ner
ve endings of the human and guinea-pig atrium are endowed with ATP-sensitiv
e K+ channels. These channels responded to agonists and antagonists under t
he experimental conditions applied and they could modulate the release of N
E thereby affecting the autonomic control of cardiac function under various
physiological and pathophysiological conditions. (C) 1999 Elsevier Science
B.V. All rights reserved.