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Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double-Blind Study

Endothelial dysfunction can predict cardiac outcomes in hypertension and reversing this abnormality has become an attractive therapeutic objective. We tested the hypothesis that blocking the angiotensin type 1 (AT(1)) receptor with valsartan in comparison with amlodipine would lead to an improvement...

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Autores principales: Tzemos, Nikolaos, Lim, Pitt O, MacDonald, Thomas M
Formato: Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948429/
https://www.ncbi.nlm.nih.gov/pubmed/19604249
http://dx.doi.org/10.1111/j.1755-5922.2009.00085.x
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author Tzemos, Nikolaos
Lim, Pitt O
MacDonald, Thomas M
author_facet Tzemos, Nikolaos
Lim, Pitt O
MacDonald, Thomas M
author_sort Tzemos, Nikolaos
collection PubMed
description Endothelial dysfunction can predict cardiac outcomes in hypertension and reversing this abnormality has become an attractive therapeutic objective. We tested the hypothesis that blocking the angiotensin type 1 (AT(1)) receptor with valsartan in comparison with amlodipine would lead to an improvement in forearm resistance artery endothelial dysfunction. In total, 25 hypertensive subjects (mean age 60 years, SD 8) with a mean daytime ambulatory blood pressure (BP) of 154 (10)/97 (6) mmHg were randomized following a 3-week placebo run-in period to a double-blind, crossover trial of 16-week treatment periods with either valsartan or amlodipine, separated by a 3-week washout period. Intra-arterial infusions of acetylcholine (ACh) and N(G)-monomethyl-L-arginine (L-NMMA) were used to assess stimulated and basal endothelium-dependent nitric oxide (NO) release, respectively. Coinfusion of ACh and L-NMMA was employed to investigate the existence of an NO-independent vasodilatory pathway. Valsartan and amlodipine each lowered the clinical BP to the same extent (139 [7]/87 [6] and 139 [11]/89 [4] mmHg, respectively). The vasodilatory response to ACh was significantly increased with valsartan (maximal percentage change in forearm blood flow (max. ΔFBF%) 301 [47] vs. 185 [34], mean [SEM]; P < 0.05) as compared with placebo, but remained unchanged with amlodipine. Both valsartan and amlodipine similarly increased the vasoconstrictive response to L-NMMA (max. ΔFBF%–43 [5], −42 [5], respectively, vs. –26 [3] baseline; P < 0.001). The vasodilatory response after coinfusion of ACh and L-NMMA was significantly (P < 0.05) enhanced only with valsartan. Valsartan reserved peripheral endothelial dysfunction through both NO-dependent and -independent pathways, while for the same degree of BP control, amlodipine had only a partial effect on NO bioactivity.
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spelling pubmed-29484292010-10-14 Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double-Blind Study Tzemos, Nikolaos Lim, Pitt O MacDonald, Thomas M Cardiovasc Ther Research Endothelial dysfunction can predict cardiac outcomes in hypertension and reversing this abnormality has become an attractive therapeutic objective. We tested the hypothesis that blocking the angiotensin type 1 (AT(1)) receptor with valsartan in comparison with amlodipine would lead to an improvement in forearm resistance artery endothelial dysfunction. In total, 25 hypertensive subjects (mean age 60 years, SD 8) with a mean daytime ambulatory blood pressure (BP) of 154 (10)/97 (6) mmHg were randomized following a 3-week placebo run-in period to a double-blind, crossover trial of 16-week treatment periods with either valsartan or amlodipine, separated by a 3-week washout period. Intra-arterial infusions of acetylcholine (ACh) and N(G)-monomethyl-L-arginine (L-NMMA) were used to assess stimulated and basal endothelium-dependent nitric oxide (NO) release, respectively. Coinfusion of ACh and L-NMMA was employed to investigate the existence of an NO-independent vasodilatory pathway. Valsartan and amlodipine each lowered the clinical BP to the same extent (139 [7]/87 [6] and 139 [11]/89 [4] mmHg, respectively). The vasodilatory response to ACh was significantly increased with valsartan (maximal percentage change in forearm blood flow (max. ΔFBF%) 301 [47] vs. 185 [34], mean [SEM]; P < 0.05) as compared with placebo, but remained unchanged with amlodipine. Both valsartan and amlodipine similarly increased the vasoconstrictive response to L-NMMA (max. ΔFBF%–43 [5], −42 [5], respectively, vs. –26 [3] baseline; P < 0.001). The vasodilatory response after coinfusion of ACh and L-NMMA was significantly (P < 0.05) enhanced only with valsartan. Valsartan reserved peripheral endothelial dysfunction through both NO-dependent and -independent pathways, while for the same degree of BP control, amlodipine had only a partial effect on NO bioactivity. Blackwell Publishing Ltd 2009 /pmc/articles/PMC2948429/ /pubmed/19604249 http://dx.doi.org/10.1111/j.1755-5922.2009.00085.x Text en © 2009 Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Research
Tzemos, Nikolaos
Lim, Pitt O
MacDonald, Thomas M
Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double-Blind Study
title Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double-Blind Study
title_full Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double-Blind Study
title_fullStr Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double-Blind Study
title_full_unstemmed Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double-Blind Study
title_short Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double-Blind Study
title_sort valsartan improves endothelial dysfunction in hypertension: a randomized, double-blind study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948429/
https://www.ncbi.nlm.nih.gov/pubmed/19604249
http://dx.doi.org/10.1111/j.1755-5922.2009.00085.x
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