This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 54/1/142    most recent HYPERTENSIONAHA.109.133710v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Briones, A. M. Articles by Salaices, M. PubMed PubMed Citation Articles by Briones, A. M. Articles by Salaices, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ATORVASTATIN HEPTANOIC ACID MALONALDEHYDE PYRROLE Related Collections Remodeling Cardiovascular Pharmacology Hypertension - basic studies Peripheral vascular disease Other Vascular biology

(Hypertension. 2009;54:142.)
© 2009 American Heart Association, Inc.

Original Articles

Atorvastatin Prevents Angiotensin II–Induced Vascular Remodeling and Oxidative Stress

Ana M. Briones; Natalia Rodríguez-Criado; Raquel Hernanz; Ana B. García-Redondo; Raul R. Rodrigues-Díez; María J. Alonso; Jesús Egido; Marta Ruiz-Ortega; Mercedes Salaices

From the Departmento de Farmacología, Facultad de Medicina (A.M.B., N.R.-C., R.H., A.B.G.-R., M.S.), and Laboratorio de Investigación Vascular y Renal (R.R.R.-D., J.E., M.R.-O.), Fundación Jiménez Díaz, Universidad Autónoma de Madrid; and the Departmento de Ciencias de la Salud III (R.H., M.J.A.), Universidad Rey Juan Carlos, Madrid, Spain.

Correspondence to Ana M. Briones, Departmento de Farmacología y Terapéutica, Facultad de Medicina, Arzobispo Morcillo 4, 28029 Madrid, Spain. E-mail ana.briones{at}uam.es

Angiotensin II (Ang II) modulates vasomotor tone, cell growth, and extracellular matrix deposition. This study analyzed the effect of atorvastatin in the possible alterations induced by Ang II on structure and mechanics of mesenteric resistance arteries and the signaling mechanisms involved. Wistar rats were infused with Ang II (100 ng/kg per day, SC minipumps, 2 weeks) with or without atorvastatin (5 mg/kg per day). Ang II increased blood pressure and plasmatic malondialdehyde levels. Compared with controls, mesenteric resistance arteries from Ang II–treated rats showed the following: (1) decreased lumen diameter; (2) increased wall/lumen; (3) decreased number of adventitial, smooth muscle, and endothelial cells; (4) increased stiffness; (5) increased collagen deposition; and (6) diminished fenestrae area and number in the internal elastic lamina. Atorvastatin did not alter blood pressure but reversed all of the structural and mechanical alterations of mesenteric arteries, including collagen and elastin alterations. In mesenteric resistance arteries, Ang II increased vascular O₂^·– production and diminished endothelial NO synthase and CuZn/superoxide dismutase but did not modify extracellular-superoxide dismutase expression. Atorvastatin improved plasmatic and vascular oxidative stress, normalized endothelial NO synthase and CuZn/superoxide dismutase expression, and increased extracellular-superoxide dismutase expression, showing antioxidant properties. Atorvastatin also diminished extracellular signal–regulated kinase 1/2 activation caused by Ang II in these vessels, indicating an interaction with Ang II–induced intracellular responses. In vascular smooth muscle cells, collagen type I release mediated by Ang II was reduced by different antioxidants and statins. Moreover, atorvastatin downregulated the Ang II–induced NADPH oxidase subunit, Nox1, expression. Our results suggest that statins might exert beneficial effects on hypertension-induced vascular remodeling by improving vascular structure, extracellular matrix alterations, and vascular stiffness. These effects might be mediated by their antioxidant properties.

Key Words: angiotensin II • atorvastatin • extracellular matrix • remodeling • oxidative stress