Rosuvastatin attenuates heart failure and cardiac remodelling in the ageing spontaneously hypertensive rat.
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.
Loch
David
D
School of Biomedical Sciences, The University of Queensland, Brisbane, Qld, Australia.
Chan
Vincent
V
Hoey
Andrew
A
Brown
Lindsay
L
D000375:Aging; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole / Q000187:drug effects; D004195:Disease Models, Animal; D004452:Echocardiography; D005464:Fluorobenzenes / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D013599:Systole / Q000187:drug effects; D020257:Ventricular Remodeling
D005464:Fluorobenzenes; D008077:Lipoproteins, LDL; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium