Effect of angiotensin receptor blockade on endothelial function: focus on olmesartan medoxomil

Figures & data

Figure 1 Atherosclerotic plaque formation in relationship to Ang II. Reprinted from the Lancet, 369, Schmeider RE, Hilgers KF, Schlaich MP. Renin-angiotensin system and cardiovascular risk, 1208–1219.¹⁰⁹ Copyright © 2007, with permission from Elsevier.

Abbreviations: ICAM-1, intercellular adhesion molecule-1; LDL, low-density lipoprotein; LOX-1, lectin-like oxidized low-density lipoprotein receptor-1; MCP-1, monocyte chemoattractant protein-1; MMP, matrix metalloproteinase; NADPH, nicotinamide adenine dinucleotide phosphate; NRB, norbormide; PAI-1, plasminogen activator inhibitor-1; TNF, tumor necrosis factor; VCAM-1, vascular cell adhesion molecule-1; VSMCs, vascular smooth muscle cells.

Table 1 Ang-(1–7) in cardiovascular disease and hypertension

Animal studies

Blockade of Ang-(1–7) dose-dependently ↑ arterial BP in salt-restricted rats^Citation89

Intracerebroventricular administration of anti-Ang-(1–7) antibodies ↑ BP in rats^Citation90

Ang-(1–7) augments baroreceptor reflex control of HR at the nucleus of the solitary tract^Citation91

Ang-(1–7) is cardioprotective in heart failure in rats induced by Ang II^Citation92

Ang-(1–7) protects against ischemic injury and arrhythmia in isolated rat hearts^Citation93,Citation94

Ang-(1–7) dilates afferent arterioles, ↑ GFR and induces natriuresis and diuresis^Citation95^–^Citation97

Ang-(1–7) ↓ neointimal proliferation after vascular injury in rat carotid arteries^Citation52

Ang-(1–7) ↓ Ang II-induced protein synthesis in cardiomyocytes^Citation56

Ang-(1–7) ↓ myocyte surface area after MI induced by coronary artery ligation in rats^Citation98

Olmesartan, but not atenolol, ↑ Ang I, Ang II, and Ang-(1–7) in SHR^Citation57

Olmesartan, but not atenolol or hydralazine, ↑ ACE2 and Ang-(1–7) and improved remodeling of the aorta in SHR^Citation55

Olmesartan and losartan ↑ ACE2 mRNA in non-infarcted ventricular tissue in rats^Citation53

Olmesartan ↑ cardiac ACE2 expression in stroke-prone SHR^Citation58

Olmesartan ↑ ACE2 immunostaining in neointima of injured carotid arteries in SHR^Citation62

Cardiac ACE2 metabolizes Ang II to Ang-(1–7) in the hearts of hypertensive rats^Citation59

Human studies

Plasma and urinary Ang-(1–7) levels are ↓ in untreated hypertensive patients^Citation99

Plasma and urinary Ang-(1–7) ↑ when BP ↓ with agents that modulate the RAAS^Citation100^–^Citation102

Abbreviations: ACE, angiotensin-converting enzyme; Ang, angiotensin; BP, blood pressure; GFR, glomerular filtration rate; HR, hypertensive rats; MI, myocardial infarction; mRNA, messenger ribonucleic acid; RAAS, renin-angiotensin-aldosterone system; SHR, spontaneously hypertensive rats.

Figure 2 The renin-angiotensin-aldosterone system. Reproduced with permission from Trask AJ, Ferrario CM. Angiotensin-(1–7): pharmacology and new perspectives in cardiovascular treatments. Cardiovasc Drug Rev. 2007;25(2):162–174.⁶⁰ Copyright © 2007. Blackwell Publishing.

Abbreviations: ACE, angiotensin-converting enzyme; Ang, angiotensin; AT₁R, angiotensin type 1 receptor; AT₂R, angiotensin type 2 receptor; NEP, neprilysin; POP, prolyl oligopeptidase; TOP, thimet oligopeptidase.

Table 2 Overview of beneficial effects of olmesartan medoxomil on endothelial function in humans

Effects of olmesartan medoxomil in humans with hypertension^Citation55^–^Citation59
Reduce vascular micro-inflammation
↓ hsCRP (vs baseline)
↓ hsTNF-α (vs baseline)
↓ IL-6 (vs baseline)
↓ MCP-1 (vs baseline)
↑ number of regenerative EPCs in peripheral blood
↓ volume of large atherosclerotic plaques (vs atenolol)
Improved endothelium-dependent coronary artery dilation
↑ change in corrected myocardial blood flow
↓ change in coronary vascular resistance from rest to after a cold pressor test as measured by positron emission tomography
Restores normal resistance vessel morphology in patients with hypertension
↓ mean augmentation index (augmentation pressure/pulse pressure), a surrogate measure of vascular compliance
↓ wall width, media cross-sectional area, and wall-to-lumen ratio of resistance arteries in gluteal subcutaneous biopsies

Abbreviations: EPC, endothelial progenitor cells; hsCRP, high-sensitivity C-reactive protein; hsTNF, high-sensitivity tumor necrosis factor; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1.

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