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

Abstract

Endothelial dysfunction is the common link between cardiovascular disease risk factors and the earliest event in the cascade of incidents that results in target organ damage. Angiotensin II, the terminal pressor effector arm of the renin-angiotensin-aldosterone system, increases blood pressure (BP) by vasoconstriction and sodium and fluid retention, and has a pro-oxidative action that induces endothelial dysfunction and contributes to vascular remodeling. Angiotensin receptor blockers (ARBs) reduce BP and morbidity and mortality in patients with hypertension, ventricular hypertrophy, diabetes mellitus, and renal disease. Olmesartan medoxomil is a long-acting, well-tolerated, effective ARB that prevents or reverses endothelial dysfunction in animal models of atherosclerosis, hypertension, diabetes, nephropathy, and retinopathy. Olmesartan medoxomil, a prodrug of olmesartan approved for the treatment of hypertension, has been shown to ameliorate endothelial dysfunction in patients with hypertension or diabetes. In randomized studies, the drug reduces vascular inflammation and the volume of large atherosclerotic plaques, increases the number of regenerative endothelial progenitor cells in the peripheral circulation, improves endothelium-dependent relaxation, and restores the normal resistance vessel morphology. Importantly, the impact of olmesartan medoxomil on endothelial dysfunction is thought to be independent of BP lowering.

Proliferative changes of renal arteriolar walls induced by administration of angiotensin II receptor blocker are frequent in juvenile rats

“…In contrast to this, dedifferentiation in the SMCs of afferent arterioles in our study is not considered to be induced by endothelial damage. A great deal of evidence has suggested that ARBs have protective effects on endothelial cells in both humans and animals, 16,17 and we found almost no morphological abnormalities in endothelial cells in the juvenile and the adult SHR+ARB groups under electron microscopy. None of the rats with these arteriolar lesions had hypertension.…”

Changes in renal vessels following the long-term administration of an angiotensin II receptor blocker in Zucker fatty rats

“…[17][18][19] ARBs are known to dilate efferent arterioles more than afferent arterioles, and to improve glomerular hypertension because AT-1 receptors exist more abundantly in the former. 20 Reports on the nephro-protective effects of ARBs are diverse in methodology; [20][21][22][23][24][25][26][27] however, few studies have concentrated on the morphology of afferent and efferent arterioles. In this study, we examined the morphology of rat renal tissue and noted a marked improvement in glomerular lesions and tubular protein casts in the ZFR+ARB group.…”

Endothelial and Vascular Smooth Cell Dysfunctions: A Comprehensive Appraisal

“…A-II increases blood pressure by vasoconstriction and sodium and fluid retention and produces overt oxidative stress resultant from the activation of NADPH oxidase, a source of ROS in blood vessels, that promotes endothelial dysfunction, inducing cytokines, chemokines and adhesion molecules secretion and contributes to vascular remodeling (Dai, D.Z. & Dai, Y., 2010;Ferrario, 2009;Partigulova & Naumov, 2010). The A-II effects on gene expression are mediated, at least in part, through the cytoplasmic NF-kB transcription factor.…”