Acute Cardiac Allograft Rejection in Nitric Oxide Synthase-2−/−and Nitric Oxide Synthase-2+/+Mice

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Effects of selective inhibitors of nitric oxide synthase-2 dimerization on acute cardiac allograft rejection.

BACKGROUND Nitric oxide synthase-2 (NOS2) is expressed during acute cardiac allograft rejection in association with myocardial inflammation, contractile dysfunction, and death of cardiomyocytes by necrosis and apoptosis. Recently, allosteric inhibitors of NOS2 monomer dimerization that block NOS2 activity have been developed. METHODS AND RESULTS To investigate effects of selective NOS2 blocka...

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Acute cardiac allograft rejection in nitric oxide synthase-2(-/-) and nitric oxide synthase-2(+/+) mice: effects of cellular chimeras on myocardial inflammation and cardiomyocyte damage and apoptosis.

BACKGROUND The contribution of nitric oxide synthase (NOS)-2 to myocardial inflammation and cardiomyocyte necrosis and apoptosis during allograft rejection was investigated through heterotopic cardiac transplantation in mice. METHODS AND RESULTS In the first experiments, hearts from C3H donor mice were transplanted into NOS-2(-/-) and NOS-2(+/+) C57BL/6J.129J recipients. A second series of ex...

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Nitric oxide synthase in cardiac sarcoplasmic reticulum.

NO. is a free radical that modulates heart function and metabolism. We report that a neuronal-type NO synthase (NOS) is located on cardiac sarcoplasmic reticulum (SR) membrane vesicles and that endogenous NO. produced by SR-associated NOS inhibits SR Ca2+ uptake. Ca2+-dependent biochemical conversion of L-arginine to L-citrulline was observed from isolated rabbit cardiac SR vesicles in the pres...

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Paul J. Cannon , Xiaochun Yang , Matthias J. Szabolcs , Stefano Ravalli , Robert R. Sciacca , Robert E. Michler b a Department of Medicine, Columbia UniÕersity College of Physicians and Surgeons, New York, NY, USA b Department of Surgery, Columbia UniÕersity College of Physicians and Surgeons, New York, NY, USA c Department of Pathology, Columbia UniÕersity College of Physicians and Surgeons, N...

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Nitric oxide (NO) regulates several cellular functions via reversible regulation of mitochondrial respiration. Nitric oxide also reacts with mitochondrial superoxide anion to produce the potent oxidative species peroxynitrite that irreversibly hinders mitochondrial activities. Recent findings demonstrating that mitochondria produce NO via mitochondrial NO synthase (mtNOS) has intrigued several ...

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ژورنال

عنوان ژورنال: Circulation

سال: 2001

ISSN: 0009-7322,1524-4539

DOI: 10.1161/01.cir.103.20.2514