Acute and Chronic Angiotensin-1 Receptor Antagonism Reverses Endothelial Dysfunction in Atherosclerosis

Prasad, Abhiram; Tupas-Habib, Theresa; Schenke, William H.; Mincemoyer, Rita; Panza, Julio A.; Waclawin, Myron A.; Ellahham, Samer; Quyyumi, Arshed A.

doi:10.1161/01.cir.101.20.2349

Cited by 182 publications

(123 citation statements)

References 34 publications

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…7 The increase of superoxide formation in the intimal layer induces endothelial dysfunction via the reduction of nitric oxide synthesis from endothelial cells. 24 In this study, the high-cholesterol diet significantly reduced relaxation induced by acetylcholine, an endothelium-dependent vasodilator, suggesting that the vascular tissues of atherosclerotic lesions show an endothelial dysfunction, which is the first step in the development of atherosclerotic plaque. The acetylcholine-induced relaxation in those monkeys fed a high-cholesterol diet was, howJournal of Human Hypertension ever, significantly improved by olmesartan.…”

Section: Discussionsupporting

confidence: 49%

See 1 more Smart Citation

Anti-atherosclerotic efficacy of olmesartan

Miyazaki

Takai

2002

J Hum Hypertens

View full text Add to dashboard Cite

The possible inhibition of lipid deposition into vascular tissues by a novel angiotensin II type 1 receptor antagonist, olmesartan, was investigated in a primate highcholesterol model. Twelve monkeys that were fed a high-cholesterol (4% cholesterol and 6% corn oil) diet for 6 months were divided into two groups: one group was given olmesartan medoxomil (10 mg/kg per day), and the other group was given no medication. A further control group of six monkeys was fed a normal diet throughout the study. The level of low-density lipoprotein (LDL) cholesterol was increased by the high-cholesterol diet, whereas that of high-density lipoprotein (HDL) cholesterol was decreased. Olmesartan decreased the areas of lipid deposition on the aortic surface and intimal cross-section area, but not the mean blood pressure and the levels of LDL and HDL cholesterol. The

show abstract

Section: Discussionsupporting

confidence: 49%

“…23,24 In the intimal layer of atherosclerotic lesions, activated macrophages induce superoxide formation via the activation of 12-or 15-lipoxygenases. 23 It is observed that smooth muscle cells activated by A II also induce NAD(P)H-dependent oxidases, which promote superoxide formation.…”

Section: Discussionmentioning

confidence: 99%

Anti-atherosclerotic efficacy of olmesartan

Miyazaki

Takai

2002

J Hum Hypertens

View full text Add to dashboard Cite

show abstract

“…28 In addition, both treatments prevent increased NO inactivation due to oxygen radicals by reducing Ang II type 1-receptor-dependent activation of the oxidant enzyme NADPH oxidase and enhancing EC-SOD activity. 29 Furthermore, an Ang II infusion reportedly resulted in increased superoxide anion production and NADPH-dependent oxidase activity, 30 leading to endothelial dysfunction in animal experiments, 31 though endothelial responses were restored by treatment with superoxide dismutase or ARB. 31 Recently, an improvement of endothelial dysfunction in hypertension has been reported to be associated with ACE2, a newly recognized homolog of ACE.…”

Section: Discussionmentioning

confidence: 99%

“…29 Furthermore, an Ang II infusion reportedly resulted in increased superoxide anion production and NADPH-dependent oxidase activity, 30 leading to endothelial dysfunction in animal experiments, 31 though endothelial responses were restored by treatment with superoxide dismutase or ARB. 31 Recently, an improvement of endothelial dysfunction in hypertension has been reported to be associated with ACE2, a newly recognized homolog of ACE. ACE2 converts Ang II to angiotensin-1-7 (Ang- (1-7)), which increased NO release from endothelial cells through its receptor Mas, thus resulting in vasodilation.…”

Section: Discussionmentioning

confidence: 99%

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

et al. 2011

View full text Add to dashboard Cite

Endothelial dysfunction in essential hypertension is an independent predictor for future cardiovascular events. Although inhibition of the renin-angiotensin system (RAS) reportedly improves endothelial function through its effects on oxidative stress and inflammation, questions remain regarding the factors that are pivotal for improvement of endothelial function by RAS inhibition. We therefore performed a prospective, randomized crossover trial in which an angiotensin II type 1 receptor antagonist, olmesartan and calcium channel blocker, amlodipine, were compared in 31 essential hypertensive patients. Results showed that, although both treatments achieved comparable lowering of blood pressure (BP), olmesartan, but not amlodipine, significantly improved endothelial function as evaluated by flow-mediated vasodilation (FMD) in the brachial artery. Although no significant changes in diabetic and lipid parameters were observed with either drug, olmesartan slightly decreased estimated glomerular filtration rate, which, surprisingly, translated into decreased microalbuminuria. In a similar vein, olmesartan reduced serum C-reactive protein and increased urine antioxidant levels compared with baseline, and reduced urine 8-epi-prostaglandin F2a levels compared with both baseline and amlodipine. Finally, although overall changes in plasma extracellular superoxide dismutase (EC-SOD) levels were not modulated by either treatment, for olmesartan there was a positive correlation between changes in FMD and those in EC-SOD levels. In conclusion, olmesartan improved endothelial function in hypertensive patients independent of its BP-lowering effect, which was due, at least in part, to its antioxidative property. Therefore, olmesartan might provide a greater long-term benefit for hypertensive patients with impaired endothelial function than amlodipine.

show abstract

“…The technique has been described in detail previously. 18 Briefly, studies were performed in a temperature-controlled room, and brachial diameter was measured above the antecubital fossa in the non-dominant arm using an 11 MHz high resolution ultrasound transducer (Acuson Inc., Malvern, PA, USA). Flow-mediated vasodilation (FMD) was determined by inflating a BP cuff on the forearm to 4200 mm Hg for 5 min, deflating rapidly, and recording brachial diameter at 1 min after onset of hyperaemia.…”

Section: Measurement Of Endothelial Functionmentioning

confidence: 99%

Tetrahydrobiopterin: a novel antihypertensive therapy

et al. 2008

View full text Add to dashboard Cite

Tetrahydrobiopterin (BH 4 ) is a cofactor for the nitric oxide (NO) synthase enzymes, such that its insufficiency results in uncoupling of the enzyme, leading to release of superoxide rather than NO in disease states, including hypertension. We hypothesized that oral BH 4 will reduce arterial blood pressure (BP) and improve endothelial function in hypertensive subjects. Oral BH 4 was given to subjects with poorly controlled hypertension (BP 4135/85 mm Hg) and weekly measurements of BP and endothelial function made. In Study 1, 5 or 10 mg kg À1 day À1 of BH 4 (n ¼ 8) was administered orally for 8 weeks, and in Study 2, 200 and 400 mg of BH 4 (n ¼ 16) was given in divided doses for 4 weeks. Study 1: significant reductions in systolic (P ¼ 0.005) and mean BP (P ¼ 0.01) were observed with both doses of BH 4 . Systolic BP was 15 ± 15 mm Hg (P ¼ 0.04) lower after 5 weeks and persisted for the 8-week study period. Study 2: subjects given 400 mg BH 4 had decreased systolic (P ¼ 0.03) and mean BP (P ¼ 0.04), with a peak decline of 16±19 mm Hg (P ¼ 0.04) at 3 weeks. BP returned to baseline 4 weeks after discontinuation. Significant improvement in endothelial function was observed in Study 1 subjects and those receiving 400 mg BH 4 . There was no significant change in subjects given the 200 mg dose. This pilot investigation indicates that oral BH 4 at a daily dose of 400 mg or higher has a significant and sustained antihypertensive effect in subjects with poorly controlled hypertension, an effect that is associated with improved endothelial NO bioavailability.

show abstract

Acute and Chronic Angiotensin-1 Receptor Antagonism Reverses Endothelial Dysfunction in Atherosclerosis

Abstract: The results of the present study indicate that inhibition of the AT(1) receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits.

Cited by 182 publications

References 34 publications

Anti-atherosclerotic efficacy of olmesartan

Anti-atherosclerotic efficacy of olmesartan

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

Tetrahydrobiopterin: a novel antihypertensive therapy

Contact Info

Product

Resources

About