Upregulation of type iii endothelial cell nitric oxide...

A - Human Necessities – 61 – K

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A61K 31/366 (2006.01) A61K 31/00 (2006.01) A61K 31/198 (2006.01) A61K 31/365 (2006.01) A61K 31/505 (2006.01) A61K 31/519 (2006.01) A61K 31/7076 (2006.01) A61K 45/06 (2006.01) A61P 9/00 (2006.01) A61P 9/10 (2006.01) C12Q 1/26 (2006.01)

Patent

CA 2368187

A new use for HMG-CoA reductase inhibitors is provided. In the instant invention, HMG-CoA reductase inhibitors are found to upregulate endothelial cell Nitric Oxide Synthase activity through a mechanism other than preventing the formation of oxidative-LDL. As a result, HMG-CoA reductase inhibitors are useful in treating or preventing conditions that result from the abnormally low expression and/or activity of endothelial cell Nitric Oxide Synthase. Such conditions include pulmonary hypertension, ischemic stroke, impotence, heart failure, hypoxia-induced conditions, insulin deficiency, progressive renal disease, gastric or esophageal motility syndrome, etc. Subjects thought to benefit mostly from such treatments include nonhyperlipidemics and nonhypercholesterolemics, but not necessarily exclude hyperlipidemics and hypercholesterolemics.

L'invention concerne une nouvelle utilisation d'inhibiteurs de la HMG-CoA réductase. Dans la présente invention, on a découvert que les inhibiteurs de la HMG-CoA réductase font une régulation positive de l'activité de l'oxyde nitrique synthase des cellules endothéliales par un mécanisme autre que celui consistant à empêcher la formation de LDL oxydantes. Par conséquent, les inhibiteurs de la HMG-CoA réductase sont utilisés dans le traitement ou la prévention des états pathologiques résultant d'une expression et/ou d'une activité anormalement faibles de l'oxyde nitrique synthase des cellules endothéliales. Ces états pathologiques comprennent l'hypertension artérielle pulmonaire, l'infarctus cérébral, l'impuissance, l'insuffisance cardiaque, les états pathologiques induits par l'hypoxie, la carence insulinique, la néphropathie évolutive, le syndrome de la motricité gastrique ou oesophagienne, etc. Les sujets susceptible de bénéficier le plus de ces traitements sont ceux atteints de non-hyperlipidémie et de non-hypercholestérolémie, sans exclure expressément les sujets atteints d'hyperlipidémie ou d'hypercholestérolémie.

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