Rosuvastatin attenuates hypertension-induced cardiovascular remodeling without affecting blood pressure in DOCA-salt hypertensive rats.
The pleiotropic effects of statins represent potential mechanisms for the treatment of end-organ damage in hypertension. This study has investigated the effects of rosuvastatin in a model of cardiovascular remodeling, the DOCA-salt hypertensive rat. Male Wistar rats weighing 300 to 330 g were uninephrectomized (UNX) or UNX and treated with DOCA (25 mg subcutaneously every fourth day) and 1% NaCl in the drinking water. Compared with UNX controls, DOCA-salt rats developed hypertension, cardiovascular hypertrophy, inflammation with perivascular and interstitial cardiac fibrosis, endothelial dysfunction, and prolongation of ventricular action potential duration at 28 days. Rosuvastatin-treated rats received 20 mg/kg/d of the drug in 10% Tween 20 by oral gavage for 32 days commencing 4 days before uninephrectomy. UNX and DOCA-salt controls received vehicle only. Rosuvastatin therapy attenuated the development of cardiovascular hypertrophy, inflammation, fibrosis, and ventricular action potential prolongation, but did not modify hypertension or vascular dysfunction. We conclude that the pleiotropic effects of rosuvastatin include attenuation of aspects of cardiovascular remodeling in the DOCA-salt model of hypertension in rats without altering systolic blood pressure.
Loch
David
D
Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, Australia.
Levick
Scott
S
Hoey
Andrew
A
Brown
Lindsay
L
D000818:Animals; D001011:Aorta / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone; D005355:Fibrosis; D005464:Fluorobenzenes / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006984:Hypertrophy; D008297:Male; D009206:Myocardium / Q000473:pathology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013449:Sulfonamides / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects*
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides; D003900:Desoxycorticosterone; D000068718:Rosuvastatin Calcium