(Hypertension. 1995;26:480-484.)
© 1995 American Heart Association, Inc.
Articles |
From the Division of Cardiovascular Sciences, St Boniface General Hospital Research Centre and Department of Anatomy, University of Manitoba, Winnipeg, Canada.
Abstract Neuropeptide Y has been shown to inhibit
contractility in the rat heart. Although the reasons
for this effect are not known, it is possible that postsynaptic
adrenergic mechanisms involving neuropeptide Y may be responsible. To
ascertain whether this neuromodulatory effect is possible for
decreasing contractility, we investigated the effect of
neuropeptide Y on agonist-stimulated contractility of
the isolated rat myocardium. Receptor binding studies of
purified cardiac membranes showed that incubating membrane in the
presence of neuropeptide Y (10-7
mol/L) decreased the number of
-/ß-adrenoceptor binding sites
without affecting the affinity of these receptors. Isolated hearts
perfused with phenylephrine
(10-5 to
10-10 mol/L) or isoproterenol
(10-5 to
10-10 mol/L) in a nonrecirculating
Langendorff setup demonstrated a significant increase in
contractility over control values, whereas no change in
contractility was observed when the hearts were
perfused with neuropeptide Y (10-7
mol/L). However, in the presence of both agonist and neuropeptide Y the
increase in contractility previously seen with agonist
alone was not evident. Comparisons made with hearts taken from aortic
banded rats yielded similar results. Although neuropeptide Y itself was
ineffective in decreasing contractility, it prevented
the agonists from stimulating contractility when
perfused together. We conclude that neuropeptide Y does not directly
decrease contractility but prevents agonist-stimulated
increases in contractility through
-/ß-adrenoceptor pathways. This neuromodulatory effect of
neuropeptide Y is unchanged in situations of increased sympathetic
activity, such as hypertension.
Key Words: neuropeptide Y receptors, adrenergic models, cardiovascular phenylephrine isoproterenol
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