Reduction of resistance artery stiffness by treatment with the AT1-receptor antagonist losartan in essential hypertension (original) (raw)
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Circulation, 2000
Background —Structural and functional alterations of the vasculature may contribute to complications of hypertension. Because angiotensin II may be pivotal in some of these vascular abnormalities, we tested the hypothesis that the angiotensin type 1 (AT 1 ) receptor antagonist losartan, in contrast to the β-blocker atenolol, would correct resistance artery abnormalities in patients with essential hypertension. Methods and Results —Nineteen untreated patients with mild essential hypertension (47±2 years, range 30 to 65 years; 57% male) were randomly assigned in double-blind fashion to losartan or atenolol treatment for 1 year. Nine age/sex-matched normotensive subjects were also studied. Both treatments reduced blood pressure to a comparable degree (losartan, from 149±4.1/101±1.6 to 128±3.6/86±2.2 mm Hg, P <0.01; atenolol, from 150±4.0/99±1.2 to 130±3.2/84±1.4 mm Hg, P <0.01). Resistance arteries (luminal diameter 150 to 350 μm) dissected from gluteal subcutaneous biopsies were...
Effect of angiotensin ii receptor blockade on arterial stiffness: beyond blood pressure reduction
American journal of hypertension, 2002
We compared the effect of losartan (50 mg/day) to hydrochlorthiazide (12.5 mg/day) on blood pressure (BP) and arterial stiffness in 11 untreated hypertensive patients aged 47 to 69 years in a 4-week single blind randomized crossover study with an intervening 4-week washout period. Both drugs produced a significant (P <.001) and similar decrease in brachial BP. Only losartan induced a significant decrease in arterial wave reflection (P <.0001), with a preferential reduction in aortic (P <.001) compared to brachial pulse pressure. Losartan also significantly increased pulse pressure amplification and reduced pulse wave velocity. These results suggest that an AT(1) receptor antagonist induces a BP independent decrease in aortic stiffness and arterial wave reflection.
Journal of Vascular Research, 2000
Converting-enzyme inhibition reduces cardiovascular hypertrophy in hypertensive subjects. Whether the blockade of angiotensin II type 1 (AT1) receptors reduces arterial hypertrophy has never been investigated. In a double-blind study versus placebo in subjects with essential hypertension, the effect of the AT1 blocker irbesartan (150 mg/day for 8 weeks) on blood pressure, wall thickness, diameter and stiffness of the common carotid and radial arteries was studied, using echotracking techniques of high resolution. With irbesartan, mean blood pressure decreased significantly and proportionally to the baseline levels of active renin, and angiotensin I and II. There was a significant decrease in radial artery wall thickness. The percent change from baseline (± SEM) was –10.51 ± 3.42 versus 6.18 ± 4.77. There was no significant change in diameter or distensibility. This effect was correlated neither to blood pressure changes nor to hormonal baseline levels of the renin-angiotensin system...
British Journal of Pharmacology, 1999
Human isolated subcutaneous arteries were studied under isometric conditions in a myograph. 2 Addition of angiotensin II (AII) induced a concentration-dependent increase in tone in isolated arteries. The active metabolite of candesartan (CV 11974), losartan and the active metabolite of losartan, E-3174 antagonized AII-induced tone in a non-competitive manner, but the AT 2 selective antagonist, PD123319, was without eect on responses to AII. The eects of candesartan, losartan and E-3174 were analysed using a classical model of non-competitive antagonism and a two-state receptor model. 3 Mechanical removal of the endothelium; pre-incubation with N o-nitro-L-arginine methyl ester hydrochloride (L-NAME); pre-incubation with indomethacin, a cyclo-oxygenase inhibitor; or preincubation with BQ 485, an endothelin antagonist; had no signi®cant eect on contractions induced by AII. 4 Our results suggest AII contracts human isolated resistance arteries by an action on AT 1 receptors and does not involve release of endothelial factors. Use of a two-state receptor model successfully described the action of the AT 1 antagonists without sacri®cing assumptions regarding the competitive nature of binding of these antagonists.
American journal of hypertension, 2002
We measured the effects of angiotensin II blockade on arterial stiffness, augmentation index (AI%), pulse wave velocity (PWV), and blood pressure (BP) in 12 hypertensive patients (mean 49 +/- 11 years) in a 4-week, randomized, cross-over study comparing valsartan 160 mg/day with captopril 100 mg/day, with a 2-week washout period. Subsequently both therapies were combined. Reductions in PWV and AI% remained significant when corrected for BP. Combined therapy reduced PWV and AI% (P < .05) more than monotherapy, even when corrected for BP. The study shows that angiotensin receptor antagonists reduce arterial stiffness in hypertension comparable with and possibly additive to angiotensin converting enzyme inhibition.