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The reversible oral P2Y(12) antagonist AZD6140 inhibits ADP-induced contractions in murine and human vasculature.

Högberg, Carl LU ; Svensson, Helen LU ; Gustafsson, Ronny LU ; Eyjolfsson, Atli LU and Erlinge, David LU (2010) In International Journal of Cardiology 142. p.187-192
Abstract
OBJECTIVES: The platelet ADP P2Y(12) receptor which is a target for the antithrombotic drug clopidogrel is also distributed on vascular smooth muscle cells and stimulate contraction. This study investigates whether AZD6140, in contrast to clopidogrel, can inhibit ADP-mediated arterial contractions. METHODS: Mice were treated with clopidogrel, 50 mg/kg, 24 and 2 h before experiment. Thoracic aorta ring segments from both clopidogrel-treated (n=5) and untreated (n=4) mice were mounted in myograph baths. Contractions of human left internal mammary arteries (IMA) and small arteries were studied in an identical manner. RESULTS: Clopidogrel treatment per os did not inhibit contractions by the stable ADP analogue 2-MeSADP (10 microM). However,... (More)
OBJECTIVES: The platelet ADP P2Y(12) receptor which is a target for the antithrombotic drug clopidogrel is also distributed on vascular smooth muscle cells and stimulate contraction. This study investigates whether AZD6140, in contrast to clopidogrel, can inhibit ADP-mediated arterial contractions. METHODS: Mice were treated with clopidogrel, 50 mg/kg, 24 and 2 h before experiment. Thoracic aorta ring segments from both clopidogrel-treated (n=5) and untreated (n=4) mice were mounted in myograph baths. Contractions of human left internal mammary arteries (IMA) and small arteries were studied in an identical manner. RESULTS: Clopidogrel treatment per os did not inhibit contractions by the stable ADP analogue 2-MeSADP (10 microM). However, addition of 1 microM AZD6140 in vitro inhibited ADP contraction (% of maximal contraction by 60 mM K(+)) both in the clopidogrel-treated, from 64% to 32% (P=0.002) and in the untreated group, from 59% to 33% (P=0.015). 2-MeSADP contractions in human IMA and small arteries were inhibited by AZD6140. CONCLUSIONS: The antiplatelet drug AZD6140 blocks the contractile effects of ADP in both murine and human vasculature. These effects of AZD6140 could be beneficial in the management of conditions in which vasospasm may play a role. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Cardiology
volume
142
pages
187 - 192
publisher
Elsevier
external identifiers
  • wos:000278652200013
  • pmid:19176251
  • scopus:77953293012
ISSN
0167-5273
DOI
10.1016/j.ijcard.2008.12.091
language
English
LU publication?
yes
id
44c93210-8e0e-49bc-b120-a1b3944c60cc (old id 1289201)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19176251?dopt=Abstract
date added to LUP
2009-02-03 12:29:42
date last changed
2018-05-29 12:15:10
@article{44c93210-8e0e-49bc-b120-a1b3944c60cc,
  abstract     = {OBJECTIVES: The platelet ADP P2Y(12) receptor which is a target for the antithrombotic drug clopidogrel is also distributed on vascular smooth muscle cells and stimulate contraction. This study investigates whether AZD6140, in contrast to clopidogrel, can inhibit ADP-mediated arterial contractions. METHODS: Mice were treated with clopidogrel, 50 mg/kg, 24 and 2 h before experiment. Thoracic aorta ring segments from both clopidogrel-treated (n=5) and untreated (n=4) mice were mounted in myograph baths. Contractions of human left internal mammary arteries (IMA) and small arteries were studied in an identical manner. RESULTS: Clopidogrel treatment per os did not inhibit contractions by the stable ADP analogue 2-MeSADP (10 microM). However, addition of 1 microM AZD6140 in vitro inhibited ADP contraction (% of maximal contraction by 60 mM K(+)) both in the clopidogrel-treated, from 64% to 32% (P=0.002) and in the untreated group, from 59% to 33% (P=0.015). 2-MeSADP contractions in human IMA and small arteries were inhibited by AZD6140. CONCLUSIONS: The antiplatelet drug AZD6140 blocks the contractile effects of ADP in both murine and human vasculature. These effects of AZD6140 could be beneficial in the management of conditions in which vasospasm may play a role.},
  author       = {Högberg, Carl and Svensson, Helen and Gustafsson, Ronny and Eyjolfsson, Atli and Erlinge, David},
  issn         = {0167-5273},
  language     = {eng},
  pages        = {187--192},
  publisher    = {Elsevier},
  series       = {International Journal of Cardiology},
  title        = {The reversible oral P2Y(12) antagonist AZD6140 inhibits ADP-induced contractions in murine and human vasculature.},
  url          = {http://dx.doi.org/10.1016/j.ijcard.2008.12.091},
  volume       = {142},
  year         = {2010},
}