Cargando…

5-HT is a potent relaxant in rat superior mesenteric veins

Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious rat when administered chronically (1 week). 5-HT does not directly relax isolated arteries, and microsphere experiments in 5-HT-infused rats suggested that 5-HT increased flow to the splanchnic bed. We hypothesized that 5-...

Descripción completa

Detalles Bibliográficos
Autores principales: Watts, Stephanie W, Darios, Emma S, Seitz, Bridget M, Thompson, Janice M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317234/
https://www.ncbi.nlm.nih.gov/pubmed/25692021
http://dx.doi.org/10.1002/prp2.103
_version_ 1782355685322784768
author Watts, Stephanie W
Darios, Emma S
Seitz, Bridget M
Thompson, Janice M
author_facet Watts, Stephanie W
Darios, Emma S
Seitz, Bridget M
Thompson, Janice M
author_sort Watts, Stephanie W
collection PubMed
description Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious rat when administered chronically (1 week). 5-HT does not directly relax isolated arteries, and microsphere experiments in 5-HT-infused rats suggested that 5-HT increased flow to the splanchnic bed. We hypothesized that 5-HT increased splanchnic flow because of direct venous relaxation; our focus was thus on the superior mesenteric vein (SMV) as an important vein in splanchnic circulation. Real-time RT-PCR, immunohistochemistry and Western analyses supported the predominant expression of the 5-HT(2B) and 5-HT(7) receptor in the SMV. The SMV was mounted in tissue baths for measurement of isometric contraction. 5-HT caused a concentration-dependent relaxation of the endothelin-1 (ET-1)-contracted vein. The threshold of 5-HT-induced venous relaxation was significantly lower than for 5-HT-induced venous contraction (∼2 vs. 700 nmol/L, respectively). A series of serotonergic agonists established in their use of receptor characterization was tested, and the following rank order of potency found for agonist-induced relaxation (receptor selectivity): 5-CT (5-HT(1)/5-HT(7))>5-HT = LP-44 (5-HT(7))>PNU109291 (5-HT(1D)) = BW723C86 (5-HT(2B)). 8-OH-DPAT (5-HT(1A/7)), CP93129 (5-HT(1B)), mCPBG (5-HT(3/4)), AS19 (5-HT(7)) and TCB-2 (5-HT(2A)) did not relax the isolated vein. Consistent with these findings, two different 5-HT(7) receptor antagonists SB 269970 and LY215840 but not the 5-HT(2B) receptor antagonist LY272015 nor the nitric oxide synthase inhibitor LNNA abolished 5-CT-induced relaxation of the isolated SMV. 5-CT (1 μg kg(−1) min(−1), sc) also reduced blood pressure over 7 days. These findings suggest that 5-HT directly relaxes the SMV primarily through activation of the 5-HT(7) receptor.
format Online
Article
Text
id pubmed-4317234
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BlackWell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-43172342015-02-17 5-HT is a potent relaxant in rat superior mesenteric veins Watts, Stephanie W Darios, Emma S Seitz, Bridget M Thompson, Janice M Pharmacol Res Perspect Original Articles Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious rat when administered chronically (1 week). 5-HT does not directly relax isolated arteries, and microsphere experiments in 5-HT-infused rats suggested that 5-HT increased flow to the splanchnic bed. We hypothesized that 5-HT increased splanchnic flow because of direct venous relaxation; our focus was thus on the superior mesenteric vein (SMV) as an important vein in splanchnic circulation. Real-time RT-PCR, immunohistochemistry and Western analyses supported the predominant expression of the 5-HT(2B) and 5-HT(7) receptor in the SMV. The SMV was mounted in tissue baths for measurement of isometric contraction. 5-HT caused a concentration-dependent relaxation of the endothelin-1 (ET-1)-contracted vein. The threshold of 5-HT-induced venous relaxation was significantly lower than for 5-HT-induced venous contraction (∼2 vs. 700 nmol/L, respectively). A series of serotonergic agonists established in their use of receptor characterization was tested, and the following rank order of potency found for agonist-induced relaxation (receptor selectivity): 5-CT (5-HT(1)/5-HT(7))>5-HT = LP-44 (5-HT(7))>PNU109291 (5-HT(1D)) = BW723C86 (5-HT(2B)). 8-OH-DPAT (5-HT(1A/7)), CP93129 (5-HT(1B)), mCPBG (5-HT(3/4)), AS19 (5-HT(7)) and TCB-2 (5-HT(2A)) did not relax the isolated vein. Consistent with these findings, two different 5-HT(7) receptor antagonists SB 269970 and LY215840 but not the 5-HT(2B) receptor antagonist LY272015 nor the nitric oxide synthase inhibitor LNNA abolished 5-CT-induced relaxation of the isolated SMV. 5-CT (1 μg kg(−1) min(−1), sc) also reduced blood pressure over 7 days. These findings suggest that 5-HT directly relaxes the SMV primarily through activation of the 5-HT(7) receptor. BlackWell Publishing Ltd 2015-02 2015-01-05 /pmc/articles/PMC4317234/ /pubmed/25692021 http://dx.doi.org/10.1002/prp2.103 Text en © 2015 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Watts, Stephanie W
Darios, Emma S
Seitz, Bridget M
Thompson, Janice M
5-HT is a potent relaxant in rat superior mesenteric veins
title 5-HT is a potent relaxant in rat superior mesenteric veins
title_full 5-HT is a potent relaxant in rat superior mesenteric veins
title_fullStr 5-HT is a potent relaxant in rat superior mesenteric veins
title_full_unstemmed 5-HT is a potent relaxant in rat superior mesenteric veins
title_short 5-HT is a potent relaxant in rat superior mesenteric veins
title_sort 5-ht is a potent relaxant in rat superior mesenteric veins
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317234/
https://www.ncbi.nlm.nih.gov/pubmed/25692021
http://dx.doi.org/10.1002/prp2.103
work_keys_str_mv AT wattsstephaniew 5htisapotentrelaxantinratsuperiormesentericveins
AT dariosemmas 5htisapotentrelaxantinratsuperiormesentericveins
AT seitzbridgetm 5htisapotentrelaxantinratsuperiormesentericveins
AT thompsonjanicem 5htisapotentrelaxantinratsuperiormesentericveins