Modulation of Contractile Function Through Neuropeptide Y Receptors During Development of Cardiomyocyte Hypertrophy.
From: Cardiovascular Research Group, School of Medicine and Dentistry, Queen’s University Belfast, Belfast, United Kingdom.
The Journal of pharmacology and experimental therapeutics
- Publish Date: Dec 2006
- ISSN: 0022-3565
- Volume: 319
- Issue: 3
- Pages: 1286-96
- Medium: Print
- Language: English
- Citation (JAMA): Allen Adrian R, Kelso Elizabeth J, Bell David, et al. Modulation of Contractile Function Through Neuropeptide Y Receptors During Development of Cardiomyocyte Hypertrophy.. J. Pharmacol. Exp. Ther. Dec 2006;319:1286-96
Abstract
Severity of left ventricular hypertrophy (LVH) correlates with elevated plasma levels of neuropeptide Y (NPY) in hypertension. NPY elicits positive and negative contractile effects in cardiomyocytes through Y(1) and Y(2) receptors, respectively. This study tested the hypothesis that NPY receptor-mediated contraction is altered during progression of LVH. Ventricular cardiomyocytes were isolated from spontaneously hypertensive rats (SHRs) pre-LVH (12 weeks), during development (16 weeks), and at established LVH (20 weeks) and age-matched normotensive Wistar Kyoto (WKY) rats. Electrically stimulated (60 V, 0.5 Hz) cell shortening was measured using edge detection and receptor expression determined at mRNA and protein level. The NPY and Y(1) receptor-selective agonist, Leu(31)Pro(34)NPY, stimulated increases in contractile amplitude, which were abolished by the Y(1) receptor-selective antagonist, BIBP3226 [R-N(2)-(diphenyl-acetyl)-N-(4-hydroxyphenyl)methyl-argininamide)], confirming Y(1) receptor involvement. Potencies of both agonists were enhanced in SHR cardiomyocytes at 20 weeks (2300- and 380-fold versus controls). Maximal responses were not attenuated. BIBP3226 unmasked a negative contraction effect of NPY, elicited over the concentration range (10(-12) to 3 x 10(-9) M) in which NPY and PYY(3-36) attenuated the positive contraction effects of isoproterenol, the potencies of which were increased in cardiomyocytes from SHRs at 20 weeks (175- and 145-fold versus controls); maximal responses were not altered. Expression of NPY-Y(1) and NPY-Y(2) receptor mRNAs was decreased (55 and 69%) in left ventricular cardiomyocytes from 20-week-old SHRs versus age-matched WKY rats; parallel decreases (32 and 80%) were observed at protein level. Enhancement of NPY potency, producing (opposing) contractile effects on cardiomyocytes together with unchanged maximal response despite reduced receptor number, enables NPY to contribute to regulating cardiac performance during compensatory LVH.
Mesh Headings (Keywords): Animals, Arginine, Calcium, Cardiotonic Agents, Cell Differentiation, Cell Separation, Cell Size, Electric Stimulation, Hypertrophy, Left Ventricular, Isoproterenol, Male, Membrane Proteins, Myocardial Contraction, Myocytes, Cardiac, Peptide YY, RNA, Messenger, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Receptors, Neuropeptide Y, Reverse Transcriptase Polymerase Chain Reaction
Check for Full Text / PubMed Unique Identifier (PMID): 16973886
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.