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5-Hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries

Chester, Adrian H; Martin, Graeme R; Bodelsson, Mikael LU ; Arneklo-Nobin, Birgitta; Tadjkarimi, Samad; Tornebrandt, Kenneth and Yacoub, Magdi H (1990) In Cardiovascular Research 24(11). p.932-937
Abstract
STUDY OBJECTIVE--The aim of the study was to investigate the receptor events that mediate the vascular effects of 5-hydroxytryptamine (5-HT) on human coronary arteries, since 5-HT has long been thought to play a role in coronary artery vasospasm. DESIGN--Recently available selective receptor agonists and antagonists were used to examine the 5-HT receptor subtypes present in human epicardial coronary arteries using in vitro organ baths. EXPERIMENTAL MATERIAL--138 segments of coronary arteries were obtained from 21 patients aged 2-66 years undergoing heart transplantation. MEASUREMENTS AND MAIN RESULTS--5-HT produced only concentration dependent contractions of coronary artery segments. No evidence was obtained for 5-HT receptors mediating... (More)
STUDY OBJECTIVE--The aim of the study was to investigate the receptor events that mediate the vascular effects of 5-hydroxytryptamine (5-HT) on human coronary arteries, since 5-HT has long been thought to play a role in coronary artery vasospasm. DESIGN--Recently available selective receptor agonists and antagonists were used to examine the 5-HT receptor subtypes present in human epicardial coronary arteries using in vitro organ baths. EXPERIMENTAL MATERIAL--138 segments of coronary arteries were obtained from 21 patients aged 2-66 years undergoing heart transplantation. MEASUREMENTS AND MAIN RESULTS--5-HT produced only concentration dependent contractions of coronary artery segments. No evidence was obtained for 5-HT receptors mediating either endothelium dependent or endothelium independent vasorelaxation. In tissue from patients without ischaemic heart disease, 5-HT effects were mimicked by (+/-)-alpha-methyl-5-HT (alpha-me-5-HT), a selective agonist at 5-HT2 receptors. In addition, the selective 5-HT1-like receptor agonist GR43175 produced contractions which achieved 30% of the maximum response to 5-HT. Responses to alpha-me-5-HT were surmountably antagonised by the non-selective antagonist methiothepin (0.1 mumol.litre-1) as well as the 5-HT2 receptor antagonist ketanserin (0.1 mumol.litre-1). In contrast GR43175 effects were resistant to blockade by ketanserin, but remained sensitive to methiothepin. Responses to the two agonists were not antagonised by the 5-HT3 receptor antagonist MDL72222 (1.0 mumol.litre-1). Vessel segments from ischaemic heart disease patients also contracted to alpha-me-5-HT and GR43175. Diseased arteries contracted with a decrease in the maximal response induced by both alpha-me-5-HT and by 90 mM K+ depolarisation compared to "normal" vessels, but the effect of GR43175 was preserved in the diseased arteries. Vascular rings adjacent to an atheromatous lesion were more reactive to GR43175 than serial segments taken distal to the lesion. CONCLUSIONS--These results show that both 5-HT1-like and 5-HT2 receptors mediate contraction of human epicardial coronary arteries and indicate that effects mediated by 5-HT1-like receptors but not 5-HT2 receptors are preserved in patients with ischaemic heart disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
5-HT1-like/5-HT2 receptor, coronary artery, human, atherosclerosis
in
Cardiovascular Research
volume
24
issue
11
pages
932 - 937
publisher
Elsevier
external identifiers
  • pmid:2272071
  • scopus:0025051329
ISSN
1755-3245
DOI
10.1093/cvr/24.11.932
language
English
LU publication?
yes
id
b9f0a235-ca50-4c84-8bb7-80038359ccbf (old id 1105068)
date added to LUP
2008-08-04 16:15:42
date last changed
2017-07-30 03:39:00
@article{b9f0a235-ca50-4c84-8bb7-80038359ccbf,
  abstract     = {STUDY OBJECTIVE--The aim of the study was to investigate the receptor events that mediate the vascular effects of 5-hydroxytryptamine (5-HT) on human coronary arteries, since 5-HT has long been thought to play a role in coronary artery vasospasm. DESIGN--Recently available selective receptor agonists and antagonists were used to examine the 5-HT receptor subtypes present in human epicardial coronary arteries using in vitro organ baths. EXPERIMENTAL MATERIAL--138 segments of coronary arteries were obtained from 21 patients aged 2-66 years undergoing heart transplantation. MEASUREMENTS AND MAIN RESULTS--5-HT produced only concentration dependent contractions of coronary artery segments. No evidence was obtained for 5-HT receptors mediating either endothelium dependent or endothelium independent vasorelaxation. In tissue from patients without ischaemic heart disease, 5-HT effects were mimicked by (+/-)-alpha-methyl-5-HT (alpha-me-5-HT), a selective agonist at 5-HT2 receptors. In addition, the selective 5-HT1-like receptor agonist GR43175 produced contractions which achieved 30% of the maximum response to 5-HT. Responses to alpha-me-5-HT were surmountably antagonised by the non-selective antagonist methiothepin (0.1 mumol.litre-1) as well as the 5-HT2 receptor antagonist ketanserin (0.1 mumol.litre-1). In contrast GR43175 effects were resistant to blockade by ketanserin, but remained sensitive to methiothepin. Responses to the two agonists were not antagonised by the 5-HT3 receptor antagonist MDL72222 (1.0 mumol.litre-1). Vessel segments from ischaemic heart disease patients also contracted to alpha-me-5-HT and GR43175. Diseased arteries contracted with a decrease in the maximal response induced by both alpha-me-5-HT and by 90 mM K+ depolarisation compared to "normal" vessels, but the effect of GR43175 was preserved in the diseased arteries. Vascular rings adjacent to an atheromatous lesion were more reactive to GR43175 than serial segments taken distal to the lesion. CONCLUSIONS--These results show that both 5-HT1-like and 5-HT2 receptors mediate contraction of human epicardial coronary arteries and indicate that effects mediated by 5-HT1-like receptors but not 5-HT2 receptors are preserved in patients with ischaemic heart disease.},
  author       = {Chester, Adrian H and Martin, Graeme R and Bodelsson, Mikael and Arneklo-Nobin, Birgitta and Tadjkarimi, Samad and Tornebrandt, Kenneth and Yacoub, Magdi H},
  issn         = {1755-3245},
  keyword      = {5-HT1-like/5-HT2 receptor,coronary artery,human,atherosclerosis},
  language     = {eng},
  number       = {11},
  pages        = {932--937},
  publisher    = {Elsevier},
  series       = {Cardiovascular Research},
  title        = {5-Hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries},
  url          = {http://dx.doi.org/10.1093/cvr/24.11.932},
  volume       = {24},
  year         = {1990},
}