P300	Molecular basis for vascular protection by atorvastatin in L-name induced accelerated hypertension.
1M.Dupuis, 1S.Nadaud, 1I.Brocheriou, 1S.Raoux, 2M.Haloui, 2L.Louedec, 3F.Capron, 2J-B.Michel, 1F.Soubrier
1INSERM Unit 525, Paris, FR; 2INSERM Unit 460, Paris, FR; 3Hôpital Pitié-Salpétrière, Paris, FR.

Objective- Chronic inhibition of nitric oxide synthesis by Nω-nitro-L-arginine methyl ester (L-NAME) induces accelerated hypertension in the Fischer 344 rats and we aimed at characterizing the effects of atorvastatin (100 mg/kg/day), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on aortic smooth muscle cells from hypertensive rats. Methods and Results- By using rat Affymetrix DNA chips, we observed that an increased recruitment of genes parallels hypertension development, associated with remodeling of the arterial wall. Cotreatment with atorvastatin strongly modifies the transcriptional profile and prevents arterial remodeling although blood pressure is slightly reduced, suggesting mechanisms independent of blood pressure levels. Among the genes modulated after 30 days of L-NAME administration, many are also regulated in L-NAME + atorvastatin group, in a way that L-NAME-induced modulation is counter-regulated by cotreatment with atorvastatin. The functional classification of these genes highlights three major biological pathways modulated in aortic media: genes regulating cell proliferation, genes involved in the extracellular matrix remodeling and genes of the NO/cGMP signaling pathway. Conclusions- Our data show that atorvastatin exerts vascular protection, at least in part by specifically antagonizing a set of genes modulated by L-NAME-induced accelerated hypertension.

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