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      Plasminogen activator inhibitor-1 antagonist TM5441 attenuates Nω-nitro-L-arginine methyl ester-induced hypertension and vascular senescence.

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          Abstract

          Long-term inhibition of nitric oxide synthase by L-arginine analogues such as N(ω)-nitro-l-arginine methyl ester (L-NAME) has been shown to induce senescence in vitro and systemic hypertension and arteriosclerosis in vivo. We previously reported that plasminogen activator inhibitor-1 (PAI-1)-deficient mice (PAI-1(-/-)) are protected against L-NAME-induced pathologies. In this study, we investigated whether a novel, orally active PAI-1 antagonist (TM5441) has a similar protective effect against L-NAME treatment. Additionally, we studied whether L-NAME can induce vascular senescence in vivo and investigated the role of PAI-1 in this process.

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          Author and article information

          Journal
          Circulation
          Circulation
          Ovid Technologies (Wolters Kluwer Health)
          1524-4539
          0009-7322
          Nov 19 2013
          : 128
          : 21
          Affiliations
          [1 ] Department of Medicine (A.E.B., M.E., S.B.M., C.E.K., D.E.V.) and Feinberg Cardiovascular Research Institute (A.E.B., S.B.M., C.E.K., D.E.V.), Northwestern University Feinberg School of Medicine, Chicago, IL; United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Miyagi, Japan (A.I., T.M.); and Conrad Prebys Center for Chemical Genomics (D.T., D.M., L.H.S.) and Cardiopathobiology Program, Diabetes and Obesity Research Center (D.M., L.H.S.), Sanford Burnham Medical Research Institute at Lake Nona, Orlando FL.
          Article
          CIRCULATIONAHA.113.003192 NIHMS542997
          10.1161/CIRCULATIONAHA.113.003192
          3933362
          24092817
          6650adea-43c8-4333-9071-21bd2641b308
          History

          aging,hypertension,nitric oxide synthase
          aging, hypertension, nitric oxide synthase

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