AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 6 1552-R1558, Copyright © 1994 by American Physiological Society
Muscarinic inhibition of cardiac norepinephrine and neuropeptide Y release during ischemia and reperfusion
A. Haunstetter, M. Haass, X. Yi, C. Kruger and W. Kubler
Department of Cardiology, University of Heidelberg, Germany.
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.
