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

Nikolaos Tzemos, Pitt O. Lim, Thomas M. MacDonald

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    Abstract

    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. delta FBF%) 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. delta FBF% -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.

    Original languageEnglish
    Pages (from-to)151-158
    Number of pages8
    JournalCardiovascular Therapeutics
    Volume27
    Issue number3
    DOIs
    Publication statusPublished - 2009

    Keywords

    • Amlodipine
    • Blood pressure
    • Endothelium
    • Nitric oxide
    • Valsartan
    • SMOOTH-MUSCLE-CELLS
    • ANGIOTENSIN-II
    • OXIDATIVE STRESS
    • AMLODIPINE
    • ACETYLCHOLINE
    • VASODILATION
    • ANTAGONISM
    • BLOCKADE
    • HEART

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