Modulation of norepinephrine release by ATP-dependent K+-channel activators and inhibitors in guinea-pig and human isolated right atrium

Katsunori Oe, B. Sperlágh, Ernô Sántha, Ida Matkó, Hideo Nagashima, Francis F. Foldes, E. Vízi

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Objective: The aim of this study was to show, whether ATP sensitive K+ channels (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 [3H]norepinephrine ([3H]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 μM), 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 μM). Diazoxide (30-300 μM), another activator of the K(ATP) channels reduced the resting release of NE, and also attenuated the evoked release at a single concentration (100 μM), and this latter action was also counteracted by glibenclamide (30 μM). Pinacidil, increased dose-dependently the resting and stimulation-revoked release of NE in a glibenclamide-sensitive manner and reversed the inhibitory effect of cromakalim (100 μM), suggesting that it acts as an antagonist. Glibenclamide (30-300 μM), by itself enhanced the stimulation-evoked release of [3H]NE, and also increased the resting release of NE. On the other hand, 5-hydroxydecanoate, an ischemia-selective inhibitor of cardiac K(ATP) channels did not change NE release. Adenosine, (30-300 μM), an A1-receptor agonist, clonidine (3 μM), an α2-adrenoceptor agonist and oxotremorine, a muscarinic receptor agonist (30 μM) all reduced the evoked release of [3H]NE, but these effects were not modified by glibenclamide (300 μM), indicating that neuronal adenosine (A1), adrenergic (α2) and muscarinic (M3) receptors do not act on K(ATP) channels. In the human right atrium, cromakalim, and diazoxide did not affect significantly the release of [3H]NE. However, glibenclamide (30-300 μM) and pinacidil (30-300 μM) enhanced dose-dependently the evoked-release of NE, and pinacidil also augmented the resting release. Conclusions: Our results indicate that sympathetic nerve endings of the human and guinea-pig atrium are endowed with ATP-sensitive K+ channels. These channels responded to agonists and antagonists under the experimental conditions applied and they could modulate the release of NE thereby affecting the autonomic control of cardiac function under various physiological and pathophysiological conditions.

Original languageEnglish
Pages (from-to)125-134
Number of pages10
JournalCardiovascular Research
Volume43
Issue number1
DOIs
Publication statusPublished - Jul 1999

Fingerprint

Heart Atria
Norepinephrine
Guinea Pigs
Adenosine Triphosphate
Glyburide
Pinacidil
Cromakalim
Diazoxide
Adenosine
Muscarinic M3 Receptors
Oxotremorine
Muscarinic Agonists
Nerve Endings
Clonidine
Muscarinic Receptors
Adrenergic Agents
Adrenergic Receptors
Ischemia

Keywords

  • ATP sensitive potassium channels
  • Atrium
  • Guinea-pig
  • Human
  • Norepinephrine
  • Release

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Modulation of norepinephrine release by ATP-dependent K+-channel activators and inhibitors in guinea-pig and human isolated right atrium. / Oe, Katsunori; Sperlágh, B.; Sántha, Ernô; Matkó, Ida; Nagashima, Hideo; Foldes, Francis F.; Vízi, E.

In: Cardiovascular Research, Vol. 43, No. 1, 07.1999, p. 125-134.

Research output: Contribution to journalArticle

Oe, Katsunori ; Sperlágh, B. ; Sántha, Ernô ; Matkó, Ida ; Nagashima, Hideo ; Foldes, Francis F. ; Vízi, E. / Modulation of norepinephrine release by ATP-dependent K+-channel activators and inhibitors in guinea-pig and human isolated right atrium. In: Cardiovascular Research. 1999 ; Vol. 43, No. 1. pp. 125-134.
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T1 - Modulation of norepinephrine release by ATP-dependent K+-channel activators and inhibitors in guinea-pig and human isolated right atrium

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AU - Sperlágh, B.

AU - Sántha, Ernô

AU - Matkó, Ida

AU - Nagashima, Hideo

AU - Foldes, Francis F.

AU - Vízi, E.

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N2 - Objective: The aim of this study was to show, whether ATP sensitive K+ channels (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 [3H]norepinephrine ([3H]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 μM), 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 μM). Diazoxide (30-300 μM), another activator of the K(ATP) channels reduced the resting release of NE, and also attenuated the evoked release at a single concentration (100 μM), and this latter action was also counteracted by glibenclamide (30 μM). Pinacidil, increased dose-dependently the resting and stimulation-revoked release of NE in a glibenclamide-sensitive manner and reversed the inhibitory effect of cromakalim (100 μM), suggesting that it acts as an antagonist. Glibenclamide (30-300 μM), by itself enhanced the stimulation-evoked release of [3H]NE, and also increased the resting release of NE. On the other hand, 5-hydroxydecanoate, an ischemia-selective inhibitor of cardiac K(ATP) channels did not change NE release. Adenosine, (30-300 μM), an A1-receptor agonist, clonidine (3 μM), an α2-adrenoceptor agonist and oxotremorine, a muscarinic receptor agonist (30 μM) all reduced the evoked release of [3H]NE, but these effects were not modified by glibenclamide (300 μM), indicating that neuronal adenosine (A1), adrenergic (α2) and muscarinic (M3) receptors do not act on K(ATP) channels. In the human right atrium, cromakalim, and diazoxide did not affect significantly the release of [3H]NE. However, glibenclamide (30-300 μM) and pinacidil (30-300 μM) enhanced dose-dependently the evoked-release of NE, and pinacidil also augmented the resting release. Conclusions: Our results indicate that sympathetic nerve endings of the human and guinea-pig atrium are endowed with ATP-sensitive K+ channels. These channels responded to agonists and antagonists under the experimental conditions applied and they could modulate the release of NE thereby affecting the autonomic control of cardiac function under various physiological and pathophysiological conditions.

AB - Objective: The aim of this study was to show, whether ATP sensitive K+ channels (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 [3H]norepinephrine ([3H]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 μM), 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 μM). Diazoxide (30-300 μM), another activator of the K(ATP) channels reduced the resting release of NE, and also attenuated the evoked release at a single concentration (100 μM), and this latter action was also counteracted by glibenclamide (30 μM). Pinacidil, increased dose-dependently the resting and stimulation-revoked release of NE in a glibenclamide-sensitive manner and reversed the inhibitory effect of cromakalim (100 μM), suggesting that it acts as an antagonist. Glibenclamide (30-300 μM), by itself enhanced the stimulation-evoked release of [3H]NE, and also increased the resting release of NE. On the other hand, 5-hydroxydecanoate, an ischemia-selective inhibitor of cardiac K(ATP) channels did not change NE release. Adenosine, (30-300 μM), an A1-receptor agonist, clonidine (3 μM), an α2-adrenoceptor agonist and oxotremorine, a muscarinic receptor agonist (30 μM) all reduced the evoked release of [3H]NE, but these effects were not modified by glibenclamide (300 μM), indicating that neuronal adenosine (A1), adrenergic (α2) and muscarinic (M3) receptors do not act on K(ATP) channels. In the human right atrium, cromakalim, and diazoxide did not affect significantly the release of [3H]NE. However, glibenclamide (30-300 μM) and pinacidil (30-300 μM) enhanced dose-dependently the evoked-release of NE, and pinacidil also augmented the resting release. Conclusions: Our results indicate that sympathetic nerve endings of the human and guinea-pig atrium are endowed with ATP-sensitive K+ channels. These channels responded to agonists and antagonists under the experimental conditions applied and they could modulate the release of NE thereby affecting the autonomic control of cardiac function under various physiological and pathophysiological conditions.

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