This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 53/4/661    most recent HYPERTENSIONAHA.108.122820v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Torrens, C. Articles by Hanson, M. A. Search for Related Content PubMed PubMed Citation Articles by Torrens, C. Articles by Hanson, M. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ATORVASTATIN CHOLESTEROL HEPTANOIC ACID PYRROLE Medline Plus Health Information Statins Vasculitis Related Collections Cardiovascular Pharmacology Animal models of human disease Peripheral vascular disease Endothelium/vascular type/nitric oxide

(Hypertension. 2009;53:661.)
© 2009 American Heart Association, Inc.

Original Articles

Atorvastatin Restores Endothelial Function in Offspring of Protein-Restricted Rats in a Cholesterol-Independent Manner

Christopher Torrens; Christopher J. Kelsall; Laura A. Hopkins; Frederick W. Anthony; Nick P. Curzen; Mark A. Hanson

From the Vascular Biology Group (C.T., C.J.K., L.A.H., F.W.A., N.P.C., M.A.H.), Institute of Developmental Sciences, School of Medicine, and Wessex Cardiothoracic Unit (N.P.C.), University of Southampton, Southampton General Hospital, Southampton, United Kingdom.

Correspondence to Christopher Torrens, Vascular Biology Group, Institute of Developmental Sciences (887), University of Southampton, School of Medicine, Southampton General Hospital, Tremona Rd, Southampton S016 6YD, United Kingdom. E-mail c.torrens{at}southampton.ac.uk

Maternal protein restriction in rats leads to endothelial dysfunction and decreased NO bioavailability in the offspring. Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) are recognized to have pleiotropic actions including increasing NO bioavailability and reducing inflammation and oxidative damage. This study assessed statin treatment on vascular function in a model of endothelial dysfunction, which is independent of dyslipidemia. Wistar rats were fed a control (18% casein) or protein-restricted (9% casein) diet throughout pregnancy. At weaning, a subset of the protein-restricted group was given atorvastatin (10 mg/kg per day) in the drinking water. At 145 days of age, offspring were euthanized by CO₂ inhalation. Plasma samples were collected for markers of inflammation, vascular reactivity of the thoracic aorta, and small mesenteric arteries were assessed on the wire myograph, and tissues were snap frozen for molecular biology analysis. Thoracic aorta endothelial-dependent vasodilatation was attenuated in the male offspring from both protein-restricted groups compared with controls (P<0.05) but was similar in females (P value not significant). Endothelial-dependent dilatation of mesenteric arteries was attenuated in male and female protein-restricted offspring (P<0.05) and was corrected by atorvastatin. Maternal protein restriction increased plasma inflammatory markers granulocyte chemotactic protein, lipocalin-2, and β₂-microglobulin in male and C-reactive protein in female offspring (P<0.05). Atorvastatin had no effect on inflammatory markers in the males but restored C-reactive protein to control levels in the females (P<0.05). Aortic and mesenteric artery mRNA levels of endothelial NO synthase, superoxide dismutase 1, and tumor necrosis factor- were unchanged. These data suggest that atorvastatin can restore endothelial function in this model, but its effects are gender specific and dependent on the vascular bed.

Key Words: statins (atorvastatin) • experimental models • fetal programming • vascular biology • endothelium • nitric oxide • inflammation

This article has been cited by other articles:

				C. Torrens, T. H. Snelling, R. Chau, M. Shanmuganathan, J. K. Cleal, K. R. Poore, D. E. Noakes, L. Poston, M. A. Hanson, and L. R. Green Effects of pre- and periconceptional undernutrition on arterial function in adult female sheep are vascular bed dependent Exp Physiol, September 1, 2009; 94(9): 1024 - 1033. [Abstract] [Full Text] [PDF]