Neuropeptide Y prevents agonist-stimulated increases in contractility.

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 alpha-/beta-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 alpha-/beta-adrenoceptor pathways. This neuromodulatory effect of neuropeptide Y is unchanged in situations of increased sympathetic activity, such as hypertension.