Muscarinic inhibition of cardiac norepinephrine and neuropeptide Y release during ischemia and reperfusion

It was the aim of the present study to characterize the modulatory effect of muscarinic agonists on the overflow of norepinephrine and neuropeptide Y (NPY) from the in situ perfused guinea pig heart, induced by electrical stimulation of the left stellate ganglion (6 Hz, 5 V, 1 min). The muscarinic a...

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Main Authors: Haunstetter, Armin (Author) , Haass, Markus (Author) , Yi, Xiaozhong (Author) , Krüger, Carsten (Author) , Kübler, Wolfgang (Author)
Format: Article (Journal)
Language:English
Published: December 1, 1994
In: American journal of physiology. Regulatory, integrative and comparative physiology
Year: 1994, Volume: 267, Issue: 6, Pages: R1552-R1558
ISSN:1522-1490
DOI:10.1152/ajpregu.1994.267.6.R1552
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1152/ajpregu.1994.267.6.R1552
Verlag, lizenzpflichtig, Volltext: https://journals.physiology.org/doi/abs/10.1152/ajpregu.1994.267.6.R1552
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Author Notes:Armin Haunstetter, Markus Haass, Xiaozhong Yi, Carsten Krüger and Wolfgang Kübler
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Summary:It was the aim of the present study to characterize the modulatory effect of muscarinic agonists on the overflow of norepinephrine and neuropeptide Y (NPY) from the in situ perfused guinea pig heart, induced by electrical stimulation of the left stellate ganglion (6 Hz, 5 V, 1 min). The muscarinic agonists oxotremorine (0.01-1 microM) and carbachol (0.1-10 microM) reduced norepinephrine and NPY overflow in a concentration-dependent manner to approximately 30% of control. The inhibitory effect of carbachol was antagonized by the unspecific muscarinic antagonist atropine (1 microM) but not by the nicotinic antagonist hexamethonium (100 microM). The M2-specific antagonist AF-DX-116BS was 25 times more potent than the M1-specific antagonist pirenzepine in antagonizing the inhibitory effect of carbachol [50% inhibitory concentration (IC50) = 0.2 microM for AF-DX-116BS; IC50 = 5.0 microM for pirenzepine]. These findings indicate that presynaptic muscarinic inhibition of stimulated norepinephrine and NPY release from the guinea pig heart is mediated mainly by activation of M2 receptors. As early as 2 min after stop-flow ischemia, the inhibitory effect of carbachol (10 microM) on the stimulation-evoked overflow of norepinephrine and NPY was lost. On reperfusion with oxygenated buffer after 10 min of stop-flow ischemia the inhibitory effect of carbachol (10 microM) on stimulation-induced norepinephrine and NPY overflow recovered within 3 min.
Item Description:Gesehen am 12.05.2025
Physical Description:Online Resource
ISSN:1522-1490
DOI:10.1152/ajpregu.1994.267.6.R1552