Research on the key mediator nitric oxide has increased exponentially over the last ten years. It is now clear that, in addition to its role within the cardiovascular system, this mediator is also implicated in the normal physiological function and disease pathology of several organs and systems. A number of the fundamental research observations are now being developed into therapeutic principles and these are being pursued through clinical trials. This is the first work summarizing, in its two volumes, the quantum leap from basic science to clinical applications emerging from this decade of research. Commencing with a historical perspective written by Robert Furchgott, the theme of volume one is the generation and biological actions of nitric oxide. Leading experts provide current overviews in the areas of nitric oxide synthase function and regulation, the biological actions of nitric oxide and the functional significance of nitric oxide synthase gene knock-out in mice. The recognized role of
Author(s): Gabor M. Rubanyi
Series: Endothelial Cell Research
Edition: 1
Publisher: CRC Press
Year: 1999
Language: English
Commentary: 39988
Pages: 378
Book Cover......Page 1
Half-Title......Page 2
Title......Page 4
Copyright......Page 5
Dedication......Page 6
Contents......Page 7
Preface......Page 10
Contributer......Page 12
INTRODUCTION......Page 19
PATHOGENESIS OF THROMBOSIS......Page 20
Platelet Adhesion......Page 21
Platelet Recruitment and Aggregation......Page 22
Fibrinolysis......Page 23
NITRIC OXIDE SYNTHESIS......Page 24
PLATELETS AND NITRIC OXIDE......Page 26
Synergy of NO with other Platelet Inhibitors......Page 28
NO AND ATHEROTHROMBOSIS......Page 29
NO AND BLEEDING DIATHESES......Page 30
PHARMACOLOGICAL ROLE OF NO DONORS IN VASCULAR THROMBOSIS......Page 31
REFERENCES......Page 32
NITRIC OXIDE AND THE REGULATION OF BLOOD PRESSURE......Page 39
NITRIC OXIDE IN SPONTANEOUS HYPERTENSION......Page 42
NITRIC OXIDE IN RENOVASCULAR HYPERTENSION......Page 46
NITRIC OXIDE IN SALT-SENSITIVE HYPERTENSION......Page 47
NITRIC OXIDE IN HUMAN HYPERTENSION......Page 48
REFERENCES......Page 50
15 Pulmonary Hypertension......Page 54
INTRODUCTION......Page 55
NITRIC OXIDE PRODUCTION BY THE PULMONARY CIRCULATION: ROLE IN CONTROL OF PULMONARY VASCULAR RESISTANCE......Page 57
Role of NO in Maintaining Normal Pulmonary Pressures......Page 58
The L-arginine-NO Pathway In Experimental Models Of Pulmonary Hypertension......Page 59
The L-arginine-NO Pathway in Human Pulmonary Hypertension......Page 61
THERAPEUTIC CONSIDERATIONS......Page 62
REFERENCES......Page 63
INTRODUCTION......Page 70
CLINICAL PRESENTATIONS OF ATHEROSCLEROSIS......Page 72
ROLE OF THE ENDOTHELIUM......Page 73
NO AND MODULATION OF MONOCYTE ADHERENCE......Page 74
ENDOTHELIAL DYSFUNCTION: ROLE IN VASCULAR DISEASE......Page 76
NO AND APOPTOSIS......Page 79
ADMA: A NEW RISK FACTOR FOR ATHEROSCLEROSIS?......Page 80
SUMMARY......Page 82
REFERENCES......Page 83
INTRODUCTION......Page 87
A. Time Course of NO Changes in Ischemia/Reperfusion......Page 88
B. Role of NO in Endothelial Adhesion Molecules......Page 91
NEUTROPHILS AND NO IN ENDOTHELIAL DYSFUNCTION AND TISSUE NECROSIS......Page 92
MICROCIRCULATORY CHANGES IN NO AND LEUKOCYTE-ENDOTHELIUM INTERACTION......Page 94
MOLECULAR MECHANISMS OF NO IN REGULATION OF CELL ADHESION MOLECULE EXPRESSION......Page 96
NO, NO DONORS AND PEROXYNITRITE IN ISCHEMIA/ REPERFUSION......Page 99
REFERENCES......Page 103
18 Nitric Oxide and Circulatory Shock......Page 108
NITRIC OXIDE AND THE PATHOPHYSIOLOGY OF ENDOTOXIN SHOCK......Page 109
PREVENTION OF THE EXPRESSION OF INOS PROTEIN......Page 111
INHIBITION OF NOS ACTIVITY......Page 112
NITRIC OXIDE SYNTHASE INHIBITION IN HUMANS WITH SEPTIC SHOCK......Page 114
ACKNOWLEDGEMENTS......Page 115
REFERENCES......Page 116
19 Kidney Diseases......Page 119
POST-ISCHEMIC ACUTE RENAL FAILURE......Page 120
UREMIA AND DIALYSIS......Page 121
GLOMERULONEPHRITIS......Page 123
DIABETES MELLITUS......Page 125
NEPHROTOXICITY OF CYCLOSPORINE A......Page 126
Glomerulosclerosis......Page 127
REFERENCES......Page 128
Preterai Labour and Preterm Birth......Page 133
NO as an Inhibitor of Uterine Contractility......Page 135
The Role of NO in Cervical Ripening and Dilatation......Page 141
NITRIC OXIDE AND PRE-ECLAMPSIA......Page 145
Effects of NOS Inhibition During Pregnancy in Animals......Page 147
In vitro and In vivo Studies on Human Pre-eclampsia......Page 150
REFERENCES......Page 151
INTRODUCTION......Page 158
CYTOKINES IN MS AND EAE......Page 159
NO in Animal Models......Page 160
Inhibitors of iNOS in EAE......Page 161
Evidence for NO-Induced Damage of Oligodendrocytes In vitro......Page 162
Inducers of NO: proinflammatory cytokines......Page 164
Modulators of NO: antiinflammatory cytokines, antioxidants, and elevators of cAMP......Page 165
Other Effects of NO on the Immune System......Page 167
NO Production by Oligodendrocytes......Page 168
Human Glial Cell NO Production......Page 169
REFERENCES......Page 170
OSTEOARTHRITIS AND CARTILAGE......Page 180
NOS IN OA-AFFECTED CARTILAGE......Page 181
SECONDARY SIGNALS INVOLVED IN MODULATION OF OA-NOS......Page 182
REGULATION OF NO AND PGE2 PRODUCTION BY IL-lb IN OA-AFFECTED CARTILAGE......Page 183
ROLE OF TNF AND CARTILAGE SNAKE VENOM LIKE PROTEASE’S (C-SVP)/TNFa CONVERTASE IN OA-CARTILAGE......Page 185
REGULATION OF NO BY IL-17 IN OA-AFFECTED CARTILAGE......Page 186
EFFECT OF NSAIDs......Page 188
A NOVEL MECHANISM OF ACTION OF TETRACYCLINES......Page 190
REFERENCES......Page 191
23 The Role of Nitric Oxide in Rheumatoid Arthritis......Page 195
NITRIC OXIDE SYNTHESIS IS INCREASED IN ARTHRITIS......Page 196
CELLULAR SOURCES OF NO IN THE ARTHRITIC JOINT......Page 197
NITRIC OXIDE AS AN IMMUNOMODULATOR......Page 198
NITRIC OXIDE AS A MODULATOR OF INFLAMMATION......Page 199
NITRIC OXIDE AND CARTILAGE METABOLISM......Page 200
NITRIC OXIDE AND THE TREATMENT OF RHEUMATOID ARTHRITIS......Page 201
REFERENCES......Page 202
NITRIC OXIDE: BIOSYNTHESIS AND SOURCES IN THE GASTROINTESTINAL TRACT......Page 206
Signal Transduction of iNOS Expression in the Gastrointestinal Tract......Page 208
Molecular Regulation of iNOS Expression in the Gastrointestinal Tract......Page 210
REGULATION OF GASTROINTESTINAL FUNCTION BY ENDOGENOUS NITRIC OXIDE......Page 211
Electrolyte and Fluid Regulation......Page 212
Gastrointestinal Motility......Page 213
Nitric Oxide and Oxygen Centered Free Radicals......Page 214
EFFECT OF NO ON INTESTINAL ENERGETICS......Page 215
ROLE OF NITRIC OXIDE IN GASTROINTESTINAL MUCOSAL INJURY......Page 216
Enteral Nitric Oxide Replacement Therapy......Page 218
Selective Inhibition of Nitric Oxide Synthase Isoforms......Page 219
FUTURE TRENDS......Page 220
REFERENCES......Page 221
HISTORICAL ROLES OF NITRIC OXIDE......Page 233
Nitric Oxide Donor Leads Provided by Established Chemistry......Page 234
Nitrate and Nitrite Esters......Page 235
Sydnonimines and Related Compounds......Page 237
Oximes......Page 239
Sulfonated Hydroxylamines and Other NO– Donors......Page 240
S-Nitrosothiols (Thionitrites)......Page 241
Diazeniumdiolates (N2O2– Compounds)......Page 242
REFERENCES......Page 244
26 Nitric Oxide Inhalation......Page 249
MECHANISM AND SITE OF ACTION......Page 250
Pulmonary Thromboembolism......Page 252
Congenital Heart Disease......Page 253
Comparative Effects......Page 257
Persistent pulmonary hypertension of the newborn......Page 258
Pneumonia......Page 259
Acute Respiratory Distress Syndrome......Page 260
Lung Transplantation......Page 262
BRONCHODILATION......Page 263
Delivery of Inhaled NO......Page 264
Monitoring......Page 266
Nitrogen dioxide......Page 267
Rebound pulmonary hypertension......Page 268
REFERENCES......Page 269
INTRODUCTION......Page 282
APPROACHES TO NOS INHIBITORS......Page 283
Arginine Analogs......Page 285
Amidine-containing Inhibitors......Page 286
Heterocyclic Inhibitors......Page 290
Active Site Models......Page 292
REFERENCES......Page 293
28 The Pharmacology of Peroxynitrite-Dependent Neurotoxicity Blockade......Page 299
INTRODUCTION......Page 300
OBJECTIVE......Page 301
Assays......Page 302
Assays......Page 306
Assay......Page 308
Assay......Page 309
REFERENCES......Page 310
29 Hemoglobin: Its Role as a Nitric Oxide Scavenger......Page 315
NO PHYSIOLOGY AND PATHOPHYSIOLOGY......Page 316
Isolated Vessel Preparations......Page 317
Cardiovascular effects......Page 318
Effects on regional blood flow......Page 322
Effect on laboratory values......Page 323
Effect on endotoxin and bacterial growth......Page 324
SUMMARY......Page 325
REFERENCES......Page 326
INTRODUCTION......Page 331
Vascular Gene Transfer......Page 332
Construction of Recombinant Adenoviral Vector Encoding Endothelial Nitric Oxide Synthase Gene......Page 334
eNOS gene transfer and cerebral vasospasm......Page 335
eNOS gene transfer and restenosis......Page 337
eNOS gene transfer and vein bypass graft failure......Page 338
eNOS gene transfer and pulmonary hypertension......Page 339
REFERENCES......Page 340
PATHOGENESIS OF INTIMAL HYPERPLASIA......Page 345
NITRIC OXIDE IN VASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY......Page 346
NITRIC OXIDE IN THE TREATMENT OF INTIMAL HYPERPLASIA......Page 348
VASCULAR GENE THERAPY......Page 349
EFFICACY OF iNOS GENE TRANSFER......Page 352
MECHANISMS BY WHICH NO INHIBITS INTIMAL HYPERPLASIA......Page 355
OTHER APPLICATIONS OF iNOS GENE TRANSFER......Page 356
REFERENCES......Page 357
Index......Page 363
