Louis J. Ignarro, PhD, is Distinguished Professor Emeritus of the Department of Molecular and Medical Pharmacology at the UCLA School of Medicine. He has broad and extensive experience in the molecular and chemical biology of the nitric oxide-cyclic GMP signaling systems. He and his basic research teams have discovered and expanded the production and actions of nitric oxide in mammalian tissues, including the protective roles of nitric oxide in preventing hypertension, stroke and myocardial infarction, and its neurotransmitter role as the mediator of erectile function in humans. For these discoveries, he was awarded the Nobel Prize in Physiology or Medicine. Bruce Freeman, PhD is the Irwin Fridovich Distinguished Professor and Chair of the Department of Pharmacology and Chemical Biology at the University of Pittsburgh School of Medicine. He has extensive experience in the biochemistry and pharmacology of nitric oxide signaling and oxidative inflammatory reactions. He and his research team have pioneered the discovery of potent inflammatory and cell signaling mediators, that are now being translated into new therapeutic strategies by Complexa, Inc.

• Perspective1. A concise history of the discovery of mammalian nitric oxide (nitrogen monoxide) biogenesis Chemical Biology2. An integrated view of the chemical biology of NO, CO, H2S and O23. Detection of nitric oxide and related species in biological systems: A state-of-the-art review4. S-nitrosothiols and nitric oxide biology and therapeutics5. Cooperative interactions between NO and H2S: Chemistry, biology, physiology, pathophysiology6. Heme protein metabolism of NO and nitriteEnzymology7. Cross-regulation between iNOS/NO and Wnt/β-catenin signaling pathways8. Regulation and physiological functions of NO-sensitive guanylyl cyclase9. Upcoupling eNOS in cardiovascular diseaseBiology/Pharmacology10. Synthesis, actions and perspectives of nitric oxide in photosynthetic organisms11. Mitochondria and nitric oxide12. Nitric oxide formation from inorganic nitrate 13. Biochemistry of molybdopterin nitrate/nitrite reductases14. NOS, NO and the red cell15. Update on nitrite reduction in ischaemic disease: Mechanisms and clinical translation16. Electrophilic Nitro-Fatty Acids: Nitric Oxide and Nitrite-Derived Signaling Mediators and New Drug Candidates17. Regulation of redox signaling by a nitrated nucleotide and reactive cysteine persulfides18. Diffusional control of nitric oxide in the vessel wall19. Asymmetric-Dimethylarginine20. The role of nitric oxide in epigenetic regulationInflammation and Pathobiology21. Peroxynitrite formation and detection in living cells22. Nitric oxide in sepsis and hemorrhagic shock: Beneficial or detrimental?23. NO signaling defects in hypertension24. Nitric oxide regulation of cardiovascular physiology and pathophysiology25. Inhaled nitric oxide: Current clinical use and future potential uses and development26. The defective arginine-nitric oxide pathway in sickle cell disease27. Aberrant nitric oxide signaling contributes to protein misfolding in neurodegenerative diseases via S-nitrosylation and tyrosine nitration28. NO in cancer: Carcinogenesis, metastases and therapy

Louis J. Ignarro, PhD, is Distinguished Professor Emeritus of the Department of Molecular and Medical Pharmacology at the UCLA School of Medicine. He has broad and extensive experience in the molecular and chemical biology of the nitric oxide-cyclic GMP signaling systems. He and his basic research teams have discovered and expanded the production and actions of nitric oxide in mammalian tissues, including the protective roles of nitric oxide in preventing hypertension, stroke and myocardial infarction, and its neurotransmitter role as the mediator of erectile function in humans. For these discoveries, he was awarded the Nobel Prize in Physiology or Medicine. Bruce Freeman, PhD is the Irwin Fridovich Distinguished Professor and Chair of the Department of Pharmacology and Chemical Biology at the University of Pittsburgh School of Medicine. He has extensive experience in the biochemistry and pharmacology of nitric oxide signaling and oxidative inflammatory reactions. He and his research team have pioneered the discovery of potent inflammatory and cell signaling mediators, that are now being translated into new therapeutic strategies by Complexa, Inc.

• Perspective1. A concise history of the discovery of mammalian nitric oxide (nitrogen monoxide) biogenesis Chemical Biology2. An integrated view of the chemical biology of NO, CO, H2S and O23. Detection of nitric oxide and related species in biological systems: A state-of-the-art review4. S-nitrosothiols and nitric oxide biology and therapeutics5. Cooperative interactions between NO and H2S: Chemistry, biology, physiology, pathophysiology6. Heme protein metabolism of NO and nitriteEnzymology7. Cross-regulation between iNOS/NO and Wnt/β-catenin signaling pathways8. Regulation and physiological functions of NO-sensitive guanylyl cyclase9. Upcoupling eNOS in cardiovascular diseaseBiology/Pharmacology10. Synthesis, actions and perspectives of nitric oxide in photosynthetic organisms11. Mitochondria and nitric oxide12. Nitric oxide formation from inorganic nitrate 13. Biochemistry of molybdopterin nitrate/nitrite reductases14. NOS, NO and the red cell15. Update on nitrite reduction in ischaemic disease: Mechanisms and clinical translation16. Electrophilic Nitro-Fatty Acids: Nitric Oxide and Nitrite-Derived Signaling Mediators and New Drug Candidates17. Regulation of redox signaling by a nitrated nucleotide and reactive cysteine persulfides18. Diffusional control of nitric oxide in the vessel wall19. Asymmetric-Dimethylarginine20. The role of nitric oxide in epigenetic regulationInflammation and Pathobiology21. Peroxynitrite formation and detection in living cells22. Nitric oxide in sepsis and hemorrhagic shock: Beneficial or detrimental?23. NO signaling defects in hypertension24. Nitric oxide regulation of cardiovascular physiology and pathophysiology25. Inhaled nitric oxide: Current clinical use and future potential uses and development26. The defective arginine-nitric oxide pathway in sickle cell disease27. Aberrant nitric oxide signaling contributes to protein misfolding in neurodegenerative diseases via S-nitrosylation and tyrosine nitration28. NO in cancer: Carcinogenesis, metastases and therapy

Louis J. Ignarro, PhD, is Distinguished Professor Emeritus of the Department of Molecular and Medical Pharmacology at the UCLA School of Medicine. He has broad and extensive experience in the molecular and chemical biology of the nitric oxide-cyclic GMP signaling systems. He and his basic research teams have discovered and expanded the production and actions of nitric oxide in mammalian tissues, including the protective roles of nitric oxide in preventing hypertension, stroke and myocardial infarction, and its neurotransmitter role as the mediator of erectile function in humans. For these discoveries, he was awarded the Nobel Prize in Physiology or Medicine. Bruce Freeman, PhD is the Irwin Fridovich Distinguished Professor and Chair of the Department of Pharmacology and Chemical Biology at the University of Pittsburgh School of Medicine. He has extensive experience in the biochemistry and pharmacology of nitric oxide signaling and oxidative inflammatory reactions. He and his research team have pioneered the discovery of potent inflammatory and cell signaling mediators, that are now being translated into new therapeutic strategies by Complexa, Inc.

• Perspective1. A concise history of the discovery of mammalian nitric oxide (nitrogen monoxide) biogenesis Chemical Biology2. An integrated view of the chemical biology of NO, CO, H2S and O23. Detection of nitric oxide and related species in biological systems: A state-of-the-art review4. S-nitrosothiols and nitric oxide biology and therapeutics5. Cooperative interactions between NO and H2S: Chemistry, biology, physiology, pathophysiology6. Heme protein metabolism of NO and nitriteEnzymology7. Cross-regulation between iNOS/NO and Wnt/β-catenin signaling pathways8. Regulation and physiological functions of NO-sensitive guanylyl cyclase9. Upcoupling eNOS in cardiovascular diseaseBiology/Pharmacology10. Synthesis, actions and perspectives of nitric oxide in photosynthetic organisms11. Mitochondria and nitric oxide12. Nitric oxide formation from inorganic nitrate 13. Biochemistry of molybdopterin nitrate/nitrite reductases14. NOS, NO and the red cell15. Update on nitrite reduction in ischaemic disease: Mechanisms and clinical translation16. Electrophilic Nitro-Fatty Acids: Nitric Oxide and Nitrite-Derived Signaling Mediators and New Drug Candidates17. Regulation of redox signaling by a nitrated nucleotide and reactive cysteine persulfides18. Diffusional control of nitric oxide in the vessel wall19. Asymmetric-Dimethylarginine20. The role of nitric oxide in epigenetic regulationInflammation and Pathobiology21. Peroxynitrite formation and detection in living cells22. Nitric oxide in sepsis and hemorrhagic shock: Beneficial or detrimental?23. NO signaling defects in hypertension24. Nitric oxide regulation of cardiovascular physiology and pathophysiology25. Inhaled nitric oxide: Current clinical use and future potential uses and development26. The defective arginine-nitric oxide pathway in sickle cell disease27. Aberrant nitric oxide signaling contributes to protein misfolding in neurodegenerative diseases via S-nitrosylation and tyrosine nitration28. NO in cancer: Carcinogenesis, metastases and therapy