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Neuropeptide Y-2 receptors are involved in enhanced neurogenic vasoconstriction in spontaneously hypertensive rats

Gradin, KA ; Buus, CL ; Li, Jia-Yi LU ; Frobert, O and Simonsen, U (2006) In British Journal of Pharmacology 148(5). p.703-713
Abstract
1 The present study addressed the role of neuropeptide (NPY) Y-2 receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Western blotting and immunohistochemistry. 2 In vasopressin-activated endothelium-intact arteries, NPY and fragments with selectivity for Y-1 receptors, [Leu(31), Pro(34)] NPY, Y-2 receptors, NPY(13-36), and rat pancreatic polypeptide evoked more pronounced contractions in segments from SHR than in Wistar Kyoto (WKY) arteries, even in the presence of the Y-1 receptor antagonist, BIBP3226 (0.3 mu M,... (More)
1 The present study addressed the role of neuropeptide (NPY) Y-2 receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Western blotting and immunohistochemistry. 2 In vasopressin-activated endothelium-intact arteries, NPY and fragments with selectivity for Y-1 receptors, [Leu(31), Pro(34)] NPY, Y-2 receptors, NPY(13-36), and rat pancreatic polypeptide evoked more pronounced contractions in segments from SHR than in Wistar Kyoto (WKY) arteries, even in the presence of the Y-1 receptor antagonist, BIBP3226 (0.3 mu M, (R)-N(2)-(diphenacetyl)-N-[(4-hydroxyphenyl) methyl]D-arginineamide). 3 In the presence of prazosin and during vasopressin activation, EFS-evoked contractions were larger in arteries from SHR compared to WKY. EFS contractions were enhanced by the Y2 receptor selective antagonist BIIE0246TF (0.5 mu M, (S)-N2-[[1-[2-[4-[(R, S)-5,11-dihydro-6(6h)-oxodibenz[b,e] azepin-11-y1]-1-piperazinyl]-2-oxoethyl]cyclo-pentyl-N-[2-[1,2-dihydro-3 ,5 (4H)-dioxo-1,2-diphenyl-3H- 1,2,4-triazol-4-yl] ethyl]- argininamide), reduced by BIBP3226, and abolished by the combination of BIBP3226 and BIIE0246TF. 4 Immunoblotting showed NPY Y-1 and Y-2 receptor expression to be similar in arteries from WKY and SHR, although a specific Y-2 receptor band at 80 kDa was detected only in arteries from WKY. 5 Immunoreaction for NPY was enhanced in arteries from SHR. In contrast to arteries from WKY, BIIE0246TF increased NPY immunoreactivity in EFS-stimulated arteries from SHR. 6 The present results suggest that postjunctional neuropeptide Y-1 and Y-2 receptors contribute to neurogenic contraction of mesenteric small arteries. Moreover, both enhanced NPY content and altered neuropeptide Y-1 and Y-2 receptor activation apparently contribute to the enhanced neurogenic contraction of arteries from SHR. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Wistar Kyoto rat, neuropeptide Y ( NPY), receptors, hypertensive rat, spontaneously, mesenteric small arteries, BII0246TF, hypertension
in
British Journal of Pharmacology
volume
148
issue
5
pages
703 - 713
publisher
Wiley
external identifiers
  • wos:000238710700017
  • scopus:33745599141
ISSN
1476-5381
DOI
10.1038/sj.bjp.0706774
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041)
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dce00948-62e4-4d60-9318-fcf88ee64464 (old id 404632)
date added to LUP
2016-04-01 16:01:27
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2022-01-28 08:44:23
@article{dce00948-62e4-4d60-9318-fcf88ee64464,
  abstract     = {{1 The present study addressed the role of neuropeptide (NPY) Y-2 receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Western blotting and immunohistochemistry. 2 In vasopressin-activated endothelium-intact arteries, NPY and fragments with selectivity for Y-1 receptors, [Leu(31), Pro(34)] NPY, Y-2 receptors, NPY(13-36), and rat pancreatic polypeptide evoked more pronounced contractions in segments from SHR than in Wistar Kyoto (WKY) arteries, even in the presence of the Y-1 receptor antagonist, BIBP3226 (0.3 mu M, (R)-N(2)-(diphenacetyl)-N-[(4-hydroxyphenyl) methyl]D-arginineamide). 3 In the presence of prazosin and during vasopressin activation, EFS-evoked contractions were larger in arteries from SHR compared to WKY. EFS contractions were enhanced by the Y2 receptor selective antagonist BIIE0246TF (0.5 mu M, (S)-N2-[[1-[2-[4-[(R, S)-5,11-dihydro-6(6h)-oxodibenz[b,e] azepin-11-y1]-1-piperazinyl]-2-oxoethyl]cyclo-pentyl-N-[2-[1,2-dihydro-3 ,5 (4H)-dioxo-1,2-diphenyl-3H- 1,2,4-triazol-4-yl] ethyl]- argininamide), reduced by BIBP3226, and abolished by the combination of BIBP3226 and BIIE0246TF. 4 Immunoblotting showed NPY Y-1 and Y-2 receptor expression to be similar in arteries from WKY and SHR, although a specific Y-2 receptor band at 80 kDa was detected only in arteries from WKY. 5 Immunoreaction for NPY was enhanced in arteries from SHR. In contrast to arteries from WKY, BIIE0246TF increased NPY immunoreactivity in EFS-stimulated arteries from SHR. 6 The present results suggest that postjunctional neuropeptide Y-1 and Y-2 receptors contribute to neurogenic contraction of mesenteric small arteries. Moreover, both enhanced NPY content and altered neuropeptide Y-1 and Y-2 receptor activation apparently contribute to the enhanced neurogenic contraction of arteries from SHR.}},
  author       = {{Gradin, KA and Buus, CL and Li, Jia-Yi and Frobert, O and Simonsen, U}},
  issn         = {{1476-5381}},
  keywords     = {{Wistar Kyoto rat; neuropeptide Y ( NPY); receptors; hypertensive rat; spontaneously; mesenteric small arteries; BII0246TF; hypertension}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{703--713}},
  publisher    = {{Wiley}},
  series       = {{British Journal of Pharmacology}},
  title        = {{Neuropeptide Y-2 receptors are involved in enhanced neurogenic vasoconstriction in spontaneously hypertensive rats}},
  url          = {{http://dx.doi.org/10.1038/sj.bjp.0706774}},
  doi          = {{10.1038/sj.bjp.0706774}},
  volume       = {{148}},
  year         = {{2006}},
}