Loch, David and Chan, Vincent and Hoey, Andrew and Brown, Lindsay (2009) Rosuvastatin attenuates heart failure and cardiac remodelling in the ageing spontaneously hypertensive rat. Basic and Clinical Pharmacology and Toxicology, 105 (4). pp. 262-270. ISSN 1742-7835
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Identification Number or DOI: doi: 10.1111/j.1742-7843.2009.00440.x
3-hydroxy-3-methylglutaryl(HMG)-Coenzyme(Co)A reductase inhibitors such as rosuvastatin may improve clinical status in patients with hypertension and heart failure. The ageing spontaneously hypertensive rat (SHR) closely mimics the chronic heart failure disease process observed in humans. This study examined the structural and functional changes in the cardiovascular system of 15-month-old SHR and normotensive Wistar-Kyoto (WKY) rats treated with rosuvastatin (20 mg/kg/day perorally) for 24 weeks. Cardiovascular structure and function were monitored serially by echocardiography. At 21 months, ex vivo Langendorff, electrophysiological or histological studies were performed. Chronic rosuvastatin treatment attenuated elevations of left ventricular wet weight (mg/g body weight: 21-month WKY, 2.30 ± 0.04; 15-month SHR, 3.03 ± 0.08; 21-month SHR, 4.09 ± 0.10; 21-month SHR + rosuvastatin, 3.50 ± 0.13), myocardial extracellular matrix content (% left ventricular area: 21-month WKY, 7.6 ± 0.5; 15-month SHR, 13.2 ± 0.8; 21-month SHR 19.6 ± 1.0; 21-month SHR with rosuvastatin 14.6 ± 1.2) and diastolic stiffness (κ: 21-month WKY, 24.9 ± 0.6; 15-month SHR, 26.4 ± 0.4; 21-month SHR, 33.1 ± 0.8; 21-month SHR + rosuvastatin, 27.5 ± 0.6) as well as attenuating the deterioration of systolic and diastolic function (fractional shortening %: 21-month WKY, 66 ± 2; 15-month SHR, 51 ± 3; 21-month SHR, 38 ± 3; 21-month SHR + rosuvastatin, 52 ± 4). There was no effect on the increased systolic blood pressure, plasma low-density lipoprotein concentrations or the prolonged action potential duration. Thus, chronic rosuvastatin treatment may attenuate myocardial dysfunction in heart failure by preventing fibrosis.
|Item Type:||Article (Commonwealth Reporting Category C)|
|Additional Information:||Copyright 2009 The Authors|
|Uncontrolled Keywords:||rosuvastatin; heart failure; cardiovascular function; diastole; echocardiography; extracellular matrix; heart electrophysiology; heart left ventricle; heart muscle|
|Fields of Research (FOR2008):||11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology|
|Subjects:||320000 Medical and Health Sciences > 320500 Pharmacology and Pharmaceutical Sciences > 320502 Basic Pharmacology|
|Socio-Economic Objective (SEO2008):||C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases|
|Deposited On:||07 Mar 2010 17:19|
|Last Modified:||16 Dec 2011 13:13|
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