Published online before print June 24, 2002, doi: 10.1161/01.HYP.0000024348.87637.6F
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(Hypertension. 2002;40:142.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Simvastatin Prevents Angiotensin II–Induced Cardiac Alteration and Oxidative Stress
From Groupe Rein Hypertension (A.M., B.J.) and Laboratoire de Nutrition Humaine et Athérogénèse (S.D., J.-P.C., B.D.), Institut Universitaire de Recherche Clinique, Université de Montpellier, France.
Correspondence to Bernard Jover, Institut Universitaire de Recherche Clinique, Groupe Rein et Hypertension, 641 Av du Doyen Gaston Giraud, 34 093 Montpellier Cedex 5, France. E-mail jover{at}iurc1.iurc.montp.inserm.fr
The influence of the HMG-CoA reductase inhibitor simvastatin was assessed on the cardiovascular alterations and production of free radicals associated with chronic angiotensin II (Ang II) infusion. Simvastatin (60 mg/kg per day PO) or placebo were given concomitantly for 10 days in Sprague-Dawley rats infused with Ang II (200 ng/kg per minute SC, osmotic pump). In addition, simvastatin or placebo was also given in vehicle-infused rats. Tail-cuff pressure and albuminuria were measured before and at the end of the treatment period. Cardiac weight, carotid structure, production of reactive oxygen species (ROS, by chemiluminescence) by polymorphonuclear leukocytes and aortic wall as well as protein and lipid oxidation products were determined at the end of the study. Ang II increased tail-cuff pressure by 56±12 mm Hg and simvastatin blunted the development of hypertension by 
70% (19±5 mm Hg). Increases in heart weight index and carotid cross-sectional area induced by Ang II were obliterated by simvastatin (3.18±0.09 versus 3.46±0.11 mg/g body wt and 0.125±0.010 versus 0.177±0.010 mm2, respectively). The Ang II–induced increases in leukocyte and aortic production of ROS as well as protein and lipid oxidation products were prevented by simvastatin. No effect of simvastatin was detected in non–Ang II–infused rats. These results indicate that simvastatin prevented the development of hypertension and cardiovascular hypertrophy together with inhibition of the induced angiotensin II production of ROS. Therefore, inhibition of HMG CoA reductase by statins may have a beneficial effect on cardiovascular alterations through its antioxidant action in experimental Ang II–dependent hypertension.
Key Words: statins • angiotensin II • hypertension, experimental • cardiovascular diseases • hypertrophy • oxygen
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