azilsartan and Atherosclerosis

We have reviewed the effects of angiotensin II type 1 receptor antagonists (ARBs) in various animal models of hypertension, atherosclerosis, cardiac function, hypertrophy and fibrosis, glucose and lipid metabolism, and renal function and morphology. Those of azilsartan and telmisartan have been included comprehensively whereas those of other ARBs have been included systematically but without intention of completeness. ARBs as a class lower blood pressure in established hypertension and prevent hypertension development in all applicable animal models except those with a markedly suppressed renin-angiotensin system; blood pressure lowering even persists for a considerable time after discontinuation of treatment. This translates into a reduced mortality, particularly in models exhibiting marked hypertension. The retrieved data on vascular, cardiac and renal function and morphology as well as on glucose and lipid metabolism are discussed to address three main questions: 1. Can ARB effects on blood vessels, heart, kidney and metabolic function be explained by blood pressure lowering alone or are they additionally directly related to blockade of the renin-angiotensin system? 2. Are they shared by other inhibitors of the renin-angiotensin system, e.g. angiotensin converting enzyme inhibitors? 3. Are some effects specific for one or more compounds within the ARB class? Taken together these data profile ARBs as a drug class with unique properties that have beneficial effects far beyond those on blood pressure reduction and, in some cases distinct from those of angiotensin converting enzyme inhibitors. The clinical relevance of angiotensin receptor-independent effects of some ARBs remains to be determined.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Animals, Genetically Modified; Antihypertensive Agents; Atherosclerosis; Benzimidazoles; Benzoates; Blood Pressure; Cardiovascular Diseases; Culture Techniques; Disease Models, Animal; Drug Therapy, Combination; Endothelium, Vascular; Gene Knockout Techniques; Glucose; Humans; Hypertension; Kidney; Lipid Metabolism; Metabolic Diseases; Oxadiazoles; Renin-Angiotensin System; Stroke; Telmisartan

Oxidized LDL(Ox-LDL) mediated endothelial dysfunction is involved in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Azilsartan is a potent agent for the treatment of hypertension as the antagonist of the angiotensin II receptor. This study will investigate whether Azilsartan possesses a beneficial effect against endothelial cell dysfunction induced by ox-LDL and explore the underlying preliminary mechanism.. Ox-LDL was applied to construct an. Firstly, the elevated expressions of LOX-1, MCP-1, and CXCL-1 induced by stimulation with ox-LDL were significantly suppressed by Azilsartan. The downregulated eNOS and reduced production of NO induced by ox-LDL were reversed by the introduction of Azilsartan. Secondly, enlarged endothelial monolayer permeability and decreased expression of occludin stimulated with ox-LDL were greatly reversed by treatment with Azilsartan but were abolished by silencing the expression of KLF2. Lastly, the inhibited expression of KLF2 induced by ox-LDL was significantly elevated by the introduction of Azilsartan.. Azilsartan might ameliorate ox-LDL-induced endothelial damage via elevating the expression of KLF2.

Topics: Atherosclerosis; Benzimidazoles; Drug Evaluation, Preclinical; Endothelium, Vascular; Gene Expression Regulation; Gene Knockdown Techniques; Human Umbilical Vein Endothelial Cells; Humans; Kruppel-Like Transcription Factors; Lipoproteins, LDL; Oxadiazoles

Advantages of the new angiotensin receptor blockers (ARBs) include once daily dosing, an absence of significant adverse reactions, well tolerated side effect profile and cost effectiveness. A growing realization is their beneficial pleotropic effects. Antihypertensive agents are widely used to reduce the risk of cardiovascular events partly beyond that of blood pressure-lowering. The RAAS, and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. For patients at high cardiovascular risk based on the results of the ONTARGET and TRANSCEND studies, telmisartan is indicated for cardiovascular prevention. Studies have shown that olmesartan medoxomil treatment may slow the progression of atherosclerosis and postpone albuminuria thereby potentially improving CV outcomes.

Topics: Albuminuria; Angiotensin II Type 1 Receptor Blockers; Atherosclerosis; Benzimidazoles; Benzoates; Cardiovascular Diseases; Humans; Hypertension; Imidazoles; Olmesartan Medoxomil; Oxadiazoles; Telmisartan; Tetrazoles; Treatment Outcome