Key result
Azilsartan reduced LV wall thickness, hypertrophy, and PAI-1, and increased cardiac output in obese insulin-resistant mice with LV pressure overload compared to vehicle controls.
Why the study?
Does azilsartan improve cardiac function and reduce hypertrophy in obese insulin-resistant mice with LV pressure overload?
Does azilsartan improve cardiac function and reduce hypertrophy in obese insulin-resistant mice with LV pressure overload?
Azilsartan reduced LV hypertrophy and improved cardiac output in a mouse model of obesity, insulin resistance, and LV pressure overload, suggesting potential utility in analogous human conditions.
Does not inform clinical use; hypothesis-generating for azilsartan in metabolic pressure-overload models.
Angiotensin II receptor blockers (ARBs) are used widely for the treatment of heart failure. However, their use in obese and insulin-resistant patients remains controversial. To clarify their potential efficacy in these conditions, we administered azilsartan medoxomil (azilsartan), a prodrug of an angiotensin II receptor blocker to mice fed a high-fat diet (HFD) with left ventricular (LV) pressure overload (aortic banding). LV fibrosis (hydroxyproline), cardiac plasminogen activator inhibitor-1 (PAI-1; a marker of profibrosis), and creatine kinase (a marker of myocardial viability and energetics) were assessed. LV wall thickness and cardiac function were assessed echocardiographically. Mice given a HFD were obese and insulin resistant. Their LV hypertrophy was accompanied by greater LV PAI-1 and reduced LV creatine kinase compared with normal diet controls. Drug treatment reduced LV wall thickness, hypertrophy, and PAI-1 and increased cardiac output after aortic banding compared with results in HFD vehicle controls. Thus, azilsartan exerted favorable biological effects on the hearts of obese insulin-resistant mice subjected to LV pressure overload consistent with its potential utility in patients with analogous conditions.
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Zaman et al. (2013) studied Obesity, insulin resistance, and left ventricular pressure overload. Azilsartan medoxomil vs. HFD vehicle controls was evaluated on LV wall thickness, hypertrophy, PAI-1, and cardiac output. Azilsartan reduced LV wall thickness, hypertrophy, and PAI-1, and increased cardiac output in obese insulin-resistant mice with LV pressure overload compared to vehicle controls.
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