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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1289201
- author
- Högberg, Carl
LU
; Svensson, Helen
LU
; Gustafsson, Ronny
LU
; Eyjolfsson, Atli
LU
and Erlinge, David
LU
- organization
- publishing date
- 2010
- 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
- pmid:19176251
- 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
- 2016-04-04 08:56:50
- date last changed
- 2022-01-29 08:01:11
@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}},
doi = {{10.1016/j.ijcard.2008.12.091}},
volume = {{142}},
year = {{2010}},
}