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Comparison of the antagonistic effects of different angiotensin II receptor blockers in human coronary arteries
Author(s) -
Pantev Emil,
Stenman Emelie,
Wackenfors Angelica,
Edvinsson Lars,
Malmsjö Malin
Publication year - 2002
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/s1388-9842(02)00166-6
Subject(s) - losartan , angiotensin ii , valsartan , candesartan , medicine , endocrinology , receptor , vasoconstriction , receptor antagonist , irbesartan , angiotensin receptor , pharmacology , antagonist , blood pressure
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 (AT 1 ) and type 2 (AT 2 ) receptor mRNA expression was examined by reverse transcriptase‐polymerase chain reaction (RT‐PCR). Results: Ang II was a potent vasoconstrictor (pEC 50 =7.7). At 1 nM of the AT 1 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 AT 1 receptor antagonists had the following order of blocking effect; EXP 3174>candesartan=valsartan>losartan. The AT 2 receptor antagonist, PD 123319 (100 nM) significantly attenuated the Ang II contraction ( E max =62% of Ang II). RT‐PCR of HCA smooth muscle cells demonstrated expression of both AT 1 and AT 2 receptor mRNA. Conclusions: Ang II contraction in HCA is mediated mainly by AT 1 but also involves AT 2 receptors. The active metabolite of losartan, EXP 3174, is the most efficacious AT 1 receptor antagonist in HCA.