Chronic treatment with pravastatin prevents early cardiovascular changes in spontaneously hypertensive rats

Abstract

This study investigates the effect of pravastatin on blood pressure, cardiovascular remodelling and impaired endothelial function induced as early signs of cardiovascular disease in young spontaneously hypertensive rats (SHR). Eight-week-old SHR were treated for 4 weeks with pravastatin (20 mg kg(-1) day(-1)). Systolic blood pressure was measured periodically during the study using the tail-cuff method. At the end of the study, the left ventricular weight /body weight ratio was used as an index of left ventricular hypertrophy (LVH). Vascular function, superoxide (O(2)(-*)) production and structure were studied in aortic rings. Lipid peroxidation was measured in plasma (thiobarbituric acid reactive substances assay). Systolic blood pressure was lower in treated SHR than in control SHR, at the end of the study (171 +/- 1 vs. 159 +/- 2 mmHg, P < 0.05), and LVH was significantly reduced by pravastatin (2.7 +/- 0.02 vs. 2.5 +/- 0.01 mg g(-1), P < 0.05). Vascular responses to sodium nitroprusside and phenylephrine were similar in both groups; nevertheless, the relaxation response to acetylcholine was higher in the treated rats (45.6 +/- 2.6 vs. 58.1 +/- 3.2 %, P < 0.05). Vascular O(2)(-*) and plasma thiobarbituric acid reactive substances were reduced by pravastatin treatment, and urinary nitrites was elevated. Finally aortic wall became thinner after pravastatin treatment. Chronic treatment with pravastatin attenuated the increase of systolic blood pressure in SHR, prevented early LVH and improved vascular structure and function. These effects were accompanied by decreased measures of oxidative stress and improvements in NO production.