Characteristics of the Actions by Which 5-hydroxytryptamine Affects Electrical and Mechanical Activities in Rabbit Jugular Vein Graft

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2012 Jan 19

PMID 22251164

Citations 2

Authors

Takashi Maekawa

Kimihiro Komori

Junko Kajikuri

Takeo Itoh

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: The vasomodulating actions of 5-HT in vein grafts, and the underlying mechanisms, remain to be fully clarified. Here, we characterized the actions by which 5-HT affects electrical and mechanical activities in rabbit autologous jugular vein grafts.

Experimental Approach: Smooth muscle cell (SMC) membrane potential and isometric tension were measured in vein grafts 4 weeks after implantation into carotid arteries. Changes in the expression of 5-HT receptor subtypes and in myosin heavy chain isoforms (SM1, SM2 and SMemb) were examined by immunohistochemistry and Western blot analysis.

Key Results: The walls of grafted veins displayed massive increases in the number of SM1- and SM2-positive SMCs. 5-HT induced a large depolarization and contraction that were each reduced by both 5-HT(2A) - and 5-HT(1B/1D) -receptor antagonists. The 5-HT-induced contraction was not modified by a 5-HT₇ -receptor antagonist. The 5-HT₇ -receptor-selective agonist AS 19 did not induce relaxation during the contraction to prostaglandin F(2α) . Immunohistochemical and Western blot analyses revealed that immunoreactive responses against 5-HT(2A) and 5-HT(1B/1D) receptors were increased in the vein graft.

Conclusions And Implications: 5-HT is able to induce a large contraction in rabbit autologous jugular vein grafts through (i) an increased number of differentiated contractile SMCs; (ii) an increased number of SMCs expressing contractile 5-HT(2A) - and 5-HT(1B/1D) receptors; and (iii) a down-regulation of the function of the relaxant SMC 5-HT₇ receptors. These changes in the vein graft may help it to resist the higher pressure present on the arterial side of the circulation.

Citing Articles

Possible roles of 5-HT in vein graft failure due to intimal hyperplasia 5-HT, nitric oxide and vein graft.

Kodama A, Itoh T, Komori K Surg Today. 2013; 44(2):213-8.

PMID: 23532320 DOI: 10.1007/s00595-013-0555-z.

Characteristics of ACh-induced hyperpolarization and relaxation in rabbit jugular vein.

Itoh T, Maekawa T, Shibayama Y Br J Pharmacol. 2012; 167(3):682-96.

PMID: 22595036 PMC: 3449270. DOI: 10.1111/j.1476-5381.2012.02038.x.

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