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Blunted pancreatic polypeptide-induced vasodilatation in mesenteric resistance vessels from spontaneously hypertensive rats.
Eur J Pharmacol. 2008 Dec 28; 601(1-3):118-23.EJ

Abstract

The present study investigated the mechanisms of vasodilatation of the human pancreatic polypeptide [cPP(1-7), NPY(19-23),Ala(31),Aib(32),Gln(34)]hPP (hPP) in mesenteric small arteries from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The arteries were isolated and mounted in microvascular myographs for isometric tension recording. In vasopressin-contracted preparations with endothelium from WKY rats, hPP evoked concentration-dependent relaxations with maximal responses of 50+/-2% (n=5). hPP relaxation was reduced by endothelial cell removal and abolished in the presence of a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine-methylester (L-NAME). hPP relaxation was blunted in segments with endothelium, and absent in segments without endothelium from SHR. The combined neuropeptide Y(1)- and Y(4)-receptor antagonist, GR23118 (Ile-Glu-Pro-Dpr-Tyr-Arg-Leu-Arg-Tyr-CONH(2)), and the neuropeptide Y(1) receptor antagonist, BIBP3226 ((R) -N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)-methyl]-arginineamide), inhibited hPP-induced vasodilatation. Calcitonin gene-related peptide (CGRP) relaxation was reduced in arteries from SHR compared to WKY. The CGRP receptor antagonist, CGRP (8-37), antagonized vasodilatation induced by CGRP and rightward shifted concentration-response curves for hPP in arteries from WKY rats. There were no differences in nerves immunoreactive for CGRP in arteries from SHR compared to WKY rats. In contrast to neuropeptide Y which evokes contraction by activation of neuropeptide Y(1) and Y(2) receptors, the present results suggest hPP evokes relaxation of mesenteric small arteries by activation of prejunctional neuropeptide Y(1)-like receptors localized in CGRP-containing nerves followed by release of CGRP and of endothelium-derived NO. hPP relaxation is blunted in arteries from SHR probably as a consequence of endothelial cell dysfunction leading to reduced efficacy of CGRP.

Authors+Show Affiliations

Institute of Neuroscience and Physiology, Section for Pharmacology, University of Göteborg, The Sahlgrenska Academy, Göteborg, Sweden. kathryn.gradin@pharm.gu.seNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18851959

Citation

Gradin, Kathryn A., et al. "Blunted Pancreatic Polypeptide-induced Vasodilatation in Mesenteric Resistance Vessels From Spontaneously Hypertensive Rats." European Journal of Pharmacology, vol. 601, no. 1-3, 2008, pp. 118-23.
Gradin KA, Li JY, Zhu H, et al. Blunted pancreatic polypeptide-induced vasodilatation in mesenteric resistance vessels from spontaneously hypertensive rats. Eur J Pharmacol. 2008;601(1-3):118-23.
Gradin, K. A., Li, J. Y., Zhu, H., & Simonsen, U. (2008). Blunted pancreatic polypeptide-induced vasodilatation in mesenteric resistance vessels from spontaneously hypertensive rats. European Journal of Pharmacology, 601(1-3), 118-23. https://doi.org/10.1016/j.ejphar.2008.09.037
Gradin KA, et al. Blunted Pancreatic Polypeptide-induced Vasodilatation in Mesenteric Resistance Vessels From Spontaneously Hypertensive Rats. Eur J Pharmacol. 2008 Dec 28;601(1-3):118-23. PubMed PMID: 18851959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blunted pancreatic polypeptide-induced vasodilatation in mesenteric resistance vessels from spontaneously hypertensive rats. AU - Gradin,Kathryn A, AU - Li,Jia-Yi, AU - Zhu,Hong, AU - Simonsen,Ulf, Y1 - 2008/09/30/ PY - 2007/08/17/received PY - 2008/09/02/revised PY - 2008/09/09/accepted PY - 2008/10/15/pubmed PY - 2009/3/4/medline PY - 2008/10/15/entrez SP - 118 EP - 23 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 601 IS - 1-3 N2 - The present study investigated the mechanisms of vasodilatation of the human pancreatic polypeptide [cPP(1-7), NPY(19-23),Ala(31),Aib(32),Gln(34)]hPP (hPP) in mesenteric small arteries from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The arteries were isolated and mounted in microvascular myographs for isometric tension recording. In vasopressin-contracted preparations with endothelium from WKY rats, hPP evoked concentration-dependent relaxations with maximal responses of 50+/-2% (n=5). hPP relaxation was reduced by endothelial cell removal and abolished in the presence of a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine-methylester (L-NAME). hPP relaxation was blunted in segments with endothelium, and absent in segments without endothelium from SHR. The combined neuropeptide Y(1)- and Y(4)-receptor antagonist, GR23118 (Ile-Glu-Pro-Dpr-Tyr-Arg-Leu-Arg-Tyr-CONH(2)), and the neuropeptide Y(1) receptor antagonist, BIBP3226 ((R) -N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)-methyl]-arginineamide), inhibited hPP-induced vasodilatation. Calcitonin gene-related peptide (CGRP) relaxation was reduced in arteries from SHR compared to WKY. The CGRP receptor antagonist, CGRP (8-37), antagonized vasodilatation induced by CGRP and rightward shifted concentration-response curves for hPP in arteries from WKY rats. There were no differences in nerves immunoreactive for CGRP in arteries from SHR compared to WKY rats. In contrast to neuropeptide Y which evokes contraction by activation of neuropeptide Y(1) and Y(2) receptors, the present results suggest hPP evokes relaxation of mesenteric small arteries by activation of prejunctional neuropeptide Y(1)-like receptors localized in CGRP-containing nerves followed by release of CGRP and of endothelium-derived NO. hPP relaxation is blunted in arteries from SHR probably as a consequence of endothelial cell dysfunction leading to reduced efficacy of CGRP. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/18851959/Blunted_pancreatic_polypeptide_induced_vasodilatation_in_mesenteric_resistance_vessels_from_spontaneously_hypertensive_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00947-3 DB - PRIME DP - Unbound Medicine ER -