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Secondhand cigarette smoke induces increased expression of contractile endothelin receptors in rat coronary arteries via a MEK1/2 sensitive mechanism

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  • Lei Cao
  • Isak Lindstedt
  • Marie-Louise Edvinsson
  • Na-Na Ping
  • Yong-Xiao Cao
  • Lars Edvinsson
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Objectives: Cigarette smoke, a strong risk factor for cardiovascular diseases, upregulates contractile endothelin (ET) receptors in coronary arteries. The present study examined the effects of second hand cigarette smoke exposure on the contractile endothelin receptors and the role of the MEK1/2 pathway in rat coronary arteries. Design: Rats were exposed to secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of a MEK1/2 inhibitor, U0126 daily for another 4 weeks. Contractile responses of isolated coronary arteries were recorded by a sensitive wire myograph. The receptor protein expression levels were examined by Western blotting. Results: The results showed that SHS in vivo caused increased expression of ET receptors ETA and ETB, and that the MEK1/2 blocker U0126 significantly reversed SHS exposure-increased ETA-mediated contractile responses and protein levels. Similar alterations were observed in ETB receptors. U0126 showed dose-dependent effects on SHS-induced response on contractile property and protein levels of the ETB receptor. However, only the higher dose U0126 (15 mg/kg) had inhibitory effects on the ETA receptor. Conclusions: Taken together, our data show that SHS increases contractile ET receptors and MEK1/2 pathway inhibitor offsets SHS exposure-induced ETA and ETB receptor upregulation in rat coronary arteries.

Original languageEnglish
JournalScandinavian cardiovascular journal : SCJ
Volume55
Issue number1
Pages (from-to)50-55
Number of pages6
ISSN1401-7431
DOIs
Publication statusPublished - 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

    Research areas

  • coronary artery, endothelin, ET receptor, MEK1/2 inhibition, rat, Second hand smoke, ETB receptor, ETA receptor, MEK1, 2 inhibition

ID: 59932452