Er aldersrelatert endoteliell dysfunksjon reversibel ved behandling med rosuvastatin? : -

Is age-related endothelial dysfunction reversible by rosuvastatin treatment? Background: Statins are known to reduce cardiovascular mortality, partially independent of their cholesterol-lowering action and still not fully understood. In this study we tried to assess the effectiveness of rosuvastatin treatment for reduction of age-related endothelial dysfunction. Methods: 32 normotensive rats from NIA (Indianapolis, USA), including 16 old (30 months) and 16 young (5 months) animals, were divided into groups getting rosuvastatin 20mg/kg daily for 8 weeks or to a control group. Afterwards, isolated rings from aorta were tested in organ chambers. We registered the endothelium dependent vasodilatation induced by adding acetylcholine and used sodium nitroprusside to test the endothelium independent vasodilatation. In addition, the influence of basal NO release and superoxide anion on the vascular tone was assessed respectively as a single response to L-NAME and as a cumulative concentration response to superoxide dismutase. Vasoconstrictive properties were measured by reactions to endothelin-1, big-endothelin-1 and norepinephrine. Results: The endothelium dependent vasodilatation was significantly lower among the old animals, but showed significantly better reactions in rats treated with rosuvastatin, while endothelium independent relaxation showed no changes. However, by L-NAME, no differences in basal vascular tone were found in any of the groups. Interestingly, with superoxide dismutase there was an increased relaxation among the old animals compared to the young ones, with non-significant effects from rosuvastatin treatment. In both groups of rosuvastatin treated animals, there was found lower vasoconstrictor response to endothelin-1, most obvious among the old animals, which also to norepinephrine showed more response than their control-group. Conclusion: This study could imply that HMG-CoA inhibition partially reduces age-related endothelial dysfunction. Suggested mechanisms are improvement of the local NO availability and inhibition of the endothelin system