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Endothelin receptor blockade improves endothelial function in atherosclerotic patients on angiotensin converting enzyme inhibition
Author(s) -
BÖHM F.,
BELTRAN E.,
PERNOW J.
Publication year - 2005
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.2005.01448.x
Subject(s) - medicine , endothelin receptor , blockade , angiotensin converting enzyme , receptor , pharmacology , endothelin 1 , enzyme inhibition , endocrinology , enzyme inhibitor , angiotensin receptor , angiotensin ii , enzyme , blood pressure , biochemistry , biology
. Objectives. Endothelin‐1 (ET‐1) and angiotensin II may contribute to endothelial dysfunction, which is associated with increased risk of events in patients with coronary artery disease. The objective was to test whether dual ET A /ET B receptor antagonism improves endothelium‐dependent vasodilatation (EDV) in atherosclerotic patients, also on treatment with angiotensin converting enzyme (ACE) inhibitor. Design and setting. EDV and endothelium‐independent vasodilatation were determined in 37 patients with atherosclerosis during measurement of forearm blood flow (FBF) with venous occlusion plethysmography. The patients were then randomized to treatment with ramipril 10 mg o.d. ( n = 21) or placebo ( n = 16) for 3 months in a double‐blind fashion. Results. Intra‐arterial infusion of the ET A receptor antagonist BQ123 and the ET B receptor antagonist BQ788 (both 10 nmol min −1 ) increased basal FBF by 42 ± 4% ( P < 0.001) and enhanced EDV ( P < 0.001). Following 3 months ramipril treatment, ET receptor blockade still enhanced EDV. Acetylcholine 10 and 30 mg min −1 increased FBF by 68 ± 12 and 64 ± 12 mL min −1 /1000 mL before vs. 101 ± 17 and 101 ± 16 mL min −1 /1000 mL following ET receptor blockade in the ramipril group ( P < 0.001). Conclusions. Dual ET A /ET B receptor blockade improves endothelial function and exerts direct vasodilator effects in patients with atherosclerosis, also on treatment with ramipril suggesting that ET receptor blockade may have important therapeutic effects when added to ACE inhibition in these patients.