Induction of Hypertrophic Responsiveness of Cardiomyocytes to Neuropeptide Y in Response to Pressure Overload

Abstract

To determine whether neuropeptide Y (NPY)-related mechanisms become activated with progression of cardiac hypertrophy in vivo, protein mass and de novo protein synthesis (incorporation of [14 C]Phe, 0.1 Ci ml Ϫ1 ) were assessed in cardiomyocytes, obtained from spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (8, 12, 16, 20, and 24 weeks of age), and cultured for 24 h. NPY (10 Ϫ8 M) increased protein mass of cardiomyocytes from 16-week-old SHRs by 9.2 Ϯ 2.1% (n ϭ 8, P Ͻ 0.05). De novo protein synthesis was increased maximally in SHRs at 12, 16, and 20 weeks (P Ͻ 0.05, n ϭ 8) in response to NPY by 12.6 Ϯ 2.1% (10 Ϫ6 M), 20.1 Ϯ 4.2% (10 Ϫ8 M), and 9.4 Ϯ 1.8% (10 Ϫ7 M), respectively. Peptide YY 3-36 ,

Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results in Cardiac Dysfunction and Hypertrophy in Rats

“…While Nicholl SM et al report that initiation of cardiomyocyte hypertrophy by NPY requires activation of both Y1 and Y2 receptors [24]. There are other reports that NPY, via Y5 receptors, induces hypertrophic responsiveness in the cardiomyocytes of spontaneously hypertensive rat [44] and potentiates phenylephrine-induced MAPK activation in primary cardiomyocytes [23]. These findings suggest that Y1, Y2 and Y5 receptors are all involved in cardiac hypertrophy and Y1 and Y2 might play consistent or opposing roles in the hypertrophic process under different study conditions.…”

“…In vitro research demonstrates that NPY induces hypertrophic responsiveness of cardiomyocytes via NPY receptors or the CaN signaling pathway [24,25,34,44]. In vivo studies are limited to the finding that plasma levels of NPY are increased and correlate with left ventricular hypertrophy in patients with hypertension or end-stage renal disease [10,27].…”

NPY and Cardiac Diseases

“…In both fetal human and adult rat hearts, NPY is expressed in right ventricular endocardial endothelial cells not only at the level of the cytosol, but also in the nucleus; endocardial endothelial cells are able to secrete NPY in response to an increase in intracellular Ca 2+ [66]. Also, in rat heart, NPY is synthesised in cardiomyocytes [67].…”

“…It remains to be established if NPY synthesised and released from other sources in the heart, such as the endocardial endothelial cells, has a differential regulation in cardiac disease states. It is known, however, that the expression of prepro-NPY is not changed in cardiomyocytes during the development or in established ventricular hypertrophy induced by pressure overload in the spontaneously hypertensive rat (SHR) [67].…”

Neuropeptide Y T1128C polymorphism

“…In vitro, NPY exerts both postjunctional inotropic and chronotropic effects on cardiac tissue involving L-type Ca 2+ currents and pacemaker currents by acting on specific pre-and postsynaptic receptors [1,7]. NPY also induces cardiac hypertrophy by stimulating cardiac myocyte growth, and angiogenic effects by promoting vascular sprouting and capillary tube formation by endothelial cells [7,8]. In vivo, the cardiovascular actions of NPY are more complex and appear to depend on the species and the site or mode of administration; these effects are often difficult to reconcile from one study to another [1].…”