Neuropeptide Y in heart failure: Cardiac depletion, arrhythmias, and ATP-sensitive potassium channels

Compensatory activation of the sympathetic nervous system in patients with heart failure results in elevated plasma levels of both norepinephrine and its co-transmitter, neuropeptide Y. The following studies were designed to investigate possible changes in cardiac neuropeptide Y stores and to determine whether these changes contribute to the susceptibility of the hypertrophied heart to arrhythmias. The possible interaction of neuropeptide Y with the adenosine triphosphate-sensitive potassium channel was also addressed.;Congestive heart failure was surgically induced in young guinea pigs via suprarenal stenosis of the abdominal aorta. Using immunohistochemical staining methods, the presence and relative density of neuropeptide Y-containing nerve fibers was compared in healthy and diseased cardiac tissues. Heart failure resulted in a reduction of the peptide which was especially prominent in the left ventricle.;Using tissue bath studies, catecholamine arrhythmias were induced in isolated left ventricular papillary muscles and atria with norepinephrine (1 x 10-6 M). Neuropeptide Y (1 x 10 -7 M) did not significantly alter norepinephrine-induced shortening of functional refractory period but did reduce the number of contractions initiated by delayed after depolarization. Neuropeptide Y also reduced the number of hypertrophied tissues that developed self-sustained tachycardia by twenty- five percent, an effect not seen in cardiac tissue from control hearts.;Lastly, the possible interaction of neuropeptide Y and the adenosine triphosphate-sensitive potassium channel was evaluated using isolated cardiac and vascular smooth muscle preparations. Neuropeptide Y had no effect on the inhibition of cardiac contractility produced by the adenosine triphosphate-sensitive potassium channel opener, lemakalim. In isolated mesenteric arteries, neuropeptide Y and the adenosine triphosphate-sensitive potassium channel antagonist, glibenclamide, produced similar reversal of the effects of lemakalim. on serotonin contractions. Unlike glibenclamide, however, neuropeptide Y potentiated the serotonin contraction itself. In an assay using spontaneously contracting portal veins, neuropeptide Y caused only partial reversal of lemakalim-induced inhibition of spontaneous activity. These data fail to support inhibition of the adenosine triphosphate-sensitive potassium channel as the mechanism of neuropeptide Y activity.;In conclusion, the depletion of neuropeptide Y from the failing heart may contribute to its heightened sensitivity to lethal arrhythmias induced by catecholamines.