Skip Navigation

European Journal of Heart Failure 2002 4(6):699-705; doi:10.1016/S1388-9842(02)00166-6
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Pantev, E.
Right arrow Articles by Malmsjö, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pantev, E.
Right arrow Articles by Malmsjö, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2002 European Society of Cardiology

Comparison of the antagonistic effects of different angiotensin II receptor blockers in human coronary arteries

Emil Pantev, Emelie Stenman, Angelica Wackenfors, Lars Edvinsson and Malin Malmsjö*

Division of Experimental Vascular Research, Department of Internal Medicine, Lund University Hospital Lund, Sweden

* Corresponding author. Experimental Vascular Research, BMC A13, SE-221 84 Lund, Sweden. Tel.: +46-733-565650; fax: +46-46-222-0616. E-mail address: malin.malmsjo{at}med.lu.se


  Abstract

Background: Angiotensin II (Ang II) is a potent vasoconstrictor and a deleterious factor in cardiovascular pathophysiology. Ang II receptor blockers (ARBs) have recently been introduced into clinical practice for treatment of hypertension and congestive heart failure.

Aims: This study was undertaken to evaluate the inhibitory effects of ARBs on vasoconstriction in humans.

Methods: Vasomotor tone was analyzed in endothelium denuded, human coronary artery (HCA) segments. Ang II type 1 (AT1) and type 2 (AT2) receptor mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR).

Results: Ang II was a potent vasoconstrictor (pEC50=7.7). At 1 nM of the AT1 receptor antagonists, candesartan and valsartan, the maximum contraction was depressed to 57 and 50% of Ang II, respectively, indicating insurmountability. Although generally considered surmountable, the presence of 100 nM losartan elicited a depression of the Ang II response to 32%. Its active metabolite, EXP 3174 (1 nM), abolished the Ang II contraction. The AT1 receptor antagonists had the following order of blocking effect; EXP 3174>candesartan=valsartan>losartan. The AT2 receptor antagonist, PD 123319 (100 nM) significantly attenuated the Ang II contraction (Emax=62% of Ang II). RT-PCR of HCA smooth muscle cells demonstrated expression of both AT1 and AT2 receptor mRNA.

Conclusions: Ang II contraction in HCA is mediated mainly by AT1 but also involves AT2 receptors. The active metabolite of losartan, EXP 3174, is the most efficacious AT1 receptor antagonist in HCA.

Key Words: Coronary circulation • Vasoconstriction • Angiotensin II • AT1 receptor • AT2 receptor

Received December 3, 2001; Revised February 22, 2002; Accepted May 1, 2002


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.