Angiotensin II type 1 receptor antagonists in animal models of vascular, cardiac, metabolic and renal disease

Abstract

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.

Adherence to Antihypertensive Medications and Stroke Risk: A Dose‐Response Meta‐Analysis

“…This meta‐analysis was based on studies in real‐world practice, and its results support the importance of improved AHM adherence in preventing stroke among patients with hypertension. Increasing evidence has indicated that AHM not only could ameliorate hypertension and improve vascular structure and function but also have neuroprotective effects, such as the regulation of endothelial NO synthase, anti‐inflammatory effects, and cerebral hemodynamics‐improving effects, which may be potential mechanisms underlying their preventative effects against stroke . The results of stratified analyses indicated that higher AHM adherence was associated with lowered risks of both IS and HS, but more remarkably in HS.…”

A systematic review of urinary bladder hypertrophy in experimental diabetes: Part 2. Comparison of animal models and functional consequences

“…The prevalence of T2DM is much greater in humans than that of T1DM, making T2DM models potentially more relevant. A wide range of animal models of T2DM exist; many of them, like human T2DM, are based on diets whereas some are hereditary. However, not all T2DM models exhibit a major increase in blood glucose.…”

miRNA-200c-3p is crucial in acute respiratory distress syndrome

“…ACE2 inactivates angiotensin II (Ang II) by cleaving it to produce Ang 1-7 [9]. Ang II binds to the Ang II type 1 and type 2 receptors with strong affinity, mediating regulation of blood pressure, body fluid balance, inflammation, cell proliferation, hypertrophy and fibrosis [10][11][12]. Reduced expression levels of ACE2 have been reported in hypertension and chronic kidney disease [13,14].…”