Relaxing and Contracting Factors: Biological and Clinical Research by Paul M. VanhoutteRelaxing and Contracting Factors: Biological and Clinical Research by Paul M. Vanhoutte

Relaxing and Contracting Factors: Biological and Clinical Research

byPaul M. Vanhoutte

Paperback | January 22, 2012

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It is an exciting task to be the editor of the first monograph covering a new area of the biomedical sciences. Since the first report in 1980 by Robert Furchgott and colleagues (see Chapter 1) of the evidence of endothelium-dependent relaxation in isolated arteries, there are ever­ increasing numbers of vascular physiologists and pharmacologists who are scraping away the endothelium to look into its role in cardiovascular con­ trol. And the more one looks, the more one discovers. Not only is the list of substances that can induce endothelium-dependent relaxations im­ pressively long, but these intriguing cells can also secrete vasoconstrictor substances. The ability of the endothelium to modulate the degree of con­ traction of the underlying smooth muscle is an ancestral property of the blood vessel wall, illustrating the logic of nature, since the endothelial cells are located in the best possible strategic location to continuously monitor the properties (chemical or physical) of the blood. And more and more data emerge suggesting that in several cardiovascular diseases per­ turbations in endothelium-dependent responses are one of the early signs of the abnormal process. Thus, the importance of endothelium-dependent responses, triggered by the intellectual curiosity of one of the pioneers of vascular physiology and pharmacology, is now recognized not only by basic scientists, but also by all concerned with the cardiovascular diseases. The purpose of this monograph is to provide them with a reference work, so that they know where to start.
Title:Relaxing and Contracting Factors: Biological and Clinical ResearchFormat:PaperbackDimensions:544 pages, 22.9 × 15.2 × 0.02 inPublished:January 22, 2012Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:1461289394

ISBN - 13:9781461289395

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Table of Contents

1 Endothelium-Dependent Relaxation in Systemic Arteries.- 1. Historical Perspective.- 1.1. The Discovery of Acetylcholine-Induced Endothelium-Dependent Relaxation.- 1.2. Other Early Findings, Conclusions, and Speculation.- 2. Recent Developments.- 2.1. The Role of Cyclic GMP in Endothelium-Dependent Relaxation.- 2.2. Additional Agents Producing Endothelium-Dependent Relaxation.- 2.3. Inhibitors of Endothelium-Dependent Relaxation.- 2.4. Further Characterization of EDRF.- References.- 2 Endothelium-Dependent Contractions in Veins and Arteries.- 1. Introduction.- 2. Metabolite(s) of Arachidonic Acid (EDCF1).- 2.1. Veins.- 2.2. Cerebral Arteries.- 3. Hypoxia.- 4. Conclusion.- References.- 3 The Nature of Endothelium-Derived Relaxing Factor.- 1. Introduction.- 2. Physical Properties.- 3. Chemical Properties.- 3.1. Experimental Approach.- 3.2. Inhibition of Antioxidants.- 3.3. Metabolism of Arachidonate and EDRF.- 4. Mechanisms of Production.- 4.1. Stimulated Release.- 4.2. Basal Release.- 5. Endogenous Inactivation.- 5.1. Hemoglobin.- 5.2. Haptoglobin-Hemoglobin Complex.- 6. Mode of Action and Inferences for the Identity of EDRF.- 7. Modulation of Vasomotor Responses by Basal Release of EDRF.- 7.1. Pharmacological Implications.- 7.2. Physiological Implications.- 7.3. Pathophysiological Implications.- 8. EDRF In Vivo.- 9. Conclusions.- References.- 4 Metabolism of Arachidonic Acid and Release of Endothelium-Derived Relaxing Factors.- 1. Introduction.- 2. Endothelial Cell Metabolism of Arachidonic Acid.- 2.1. Cyclooxygenase Pathways.- 2.2. Lipoxygenase Pathways.- 2.3. Cytochrome P-450 Pathways.- 3. Evidence Relating Arachidonate Metabolites to EDRF.- 3.1. Inhibition of Arachidonic Acid Metabolism.- 3.2. Involvement of Phospholipase and Calcium Dependence.- 3.3. Exogenous Arachidonic Acid Studies.- 3.4. Melittin and Endogenous Arachidonate Studies.- 3.5. Antioxidants and Nonspecific Radical Scavengers.- 3.6. Electron Spin Resonance Spectroscopy.- 4. Evidence Against Arachidonate Metabolite Hypothesis.- 4.1. Nonspecific Action of Many Blockers.- 4.2. Other Fatty Acids Cause Endothelium-Dependent Relaxation.- 4.3. Possible Hydrophilic Nature of EDRF.- 4.4. Exogenous Application of Arachidonate Metabolites.- 5. Future Studies of Endothelium-Derived Relaxing Factor(s).- References.- 5 Modulation of the Release and Biological Activity of Endothelium-Derived Relaxing Factor by Oxygen-Derived Free Radicals.- 1. Introduction.- 2. Direct Actions on Vascular Smooth Muscle.- 3. Adrenergic Neurotransmission.- 4. Endothelium-Dependent Relaxations.- 4.1. Endothelium-Derived Relaxing Factor(s) Is Not Likely To Be an Oxygen-Derived Free Radical.- 4.2. Hydrogen Peroxide Triggers the Release of Endothelium-Derived Relaxing Factor(s).- 4.3. Hydroxyl Radical Facilitates and Superoxide Anion Inhibits Endothelium-Dependent Relaxations to Acetylcholine.- 4.4. Superoxide Anions Inactivate Endothelium-Derived Relaxing Factors.- 5. Conclusions.- References.- 6 Endothelial Cells in Culture and Production of Endothelium-Derived Relaxing Factor.- 1. Introduction.- 2. Isolation of EDRF.- 2.1. Endothelial Cells in Culture.- 2.2. Culture of Endothelial Cells on Microcarrier Beads.- 2.3. Release of EDRF from Endothelial Cells Grown on Microcarrier Beads.- 3. Properties of EDRF.- 3.1. Half-Life In Vitro: Its Estimation by the Analysis of Concentration-Relaxation Curves.- 3.2. Other Properties of EDRF Released from Cultured Endothelial Cells.- 4. Whole Artery as a Source of EDRF-A Comparison with Cells in Culture.- 5. Concluding Remarks.- References.- 7 Endothelial Cells in Culture and Production of Endothelium-Derived Constricting Factors.- 1. Introduction.- 2. Evidence for the Presence of Constricting Factors in Vascular Endothelium.- 3. Endothelium-Derived Constricting Factor(s) Produced by Endothelial Cells in Culture.- 3.1. Methodology for Studying EDCF.- 3.2. Endothelial Cell Source, Culture Conditions, and Time Course of Production of EDCF.- 3.3. Physiological Response to EDCF.- 3.4. Biochemical and Pharmacological Characterization of EDCF.- 3.5. Potential Mechanism(s) of Action of EDCF on Vascular Smooth Muscle.- 4. Effect of Hypoxia on EDCF Release.- 5. Concluding Remarks.- References.- 8 Basal Release of Endothelium-Derived Relaxing Factor.- 1. Scope.- 2. Detection of Basal EDRF Release.- 2.1. Cascade Bioassay Experiments.- 2.2. Basal EDRF Release and Cyclic GMP.- 2.3. Calcium Dependency.- 2.4. Potentiating Action of Phosphodiesterase Inhibitors.- 3. Endothelium-Dependent Depression of Vasoconstrictor Responses.- 3.1. EDRF Release Elicited by Vasoconstrictor Agents.- 3.2. Depression of Alpha-Adrenergic Contractions by Spontaneously Released EDRF in the Rat Aorta.- 3.3. Hemoglobin and Methylene Blue.- 3.4. Efficacy of Alpha-Adrenergic Agonists.- 3.5. Aorta of the Rabbit.- 4. Depression of Resting and Stimulated 45C2+ Influx by Spontaneously Released EDRF.- 5. Hypoxia-Induced Endothelium-Dependent Reponses.- 6. Differences in Basal EDRF Release.- 7. Basal EDRF Release and Vasospasm.- 8. Concluding Remarks.- References.- 9 Calcium Transport Mechanisms in Endothelial Cells Regulating the Synthesis and Release of Endothelium-Derived Relaxing Factor.- 1. Introduction.- 2. Influx of Extracellular Ca2+.- 2.1. Removal of Extracellular Ca2+.- 2.2. Ca2+ Channel Agonists.- 2.3. Ca2+ Channel Antagonists.- 2.4. Na+-Ca2+ Exchange.- 3. Liberation of Ca2+ from Intracellular Pools.- 4. Concluding Remarks.- References.- 10 Release of Endothelium-Derived Relaxing Factor(s) by Physicochemical Stimuli Eberhard Bassenge, Rudi Busse, and Ulrich Pohl.- 1. Introduction.- 2. EDRF Release and Vascular Response: Asymmetrie Behavior of the Vascular Wall.- 2.1. Bipolar Release.- 2.2. Differential Response of Inner and Outer Smooth Muscle to EDRF.- 2.3. Transmural Endothelial Stimulation.- 3. Flow-Rate and Regulation of Vascular Tone.- 3.1. Vasomotion of Arteries in Response to Changes in Flow Rate.- 3.2. Endothelial Cells as Flow Sensors.- 3.3. Physiological Relevance of Flow-Dependent Dilation.- 3.4. Effect of Long-Term Alterations in Flow Rate on Vascular Caliber.- 4. Pulsatile Flow and Release of Endothelium-Derived Vasodilators.- 4.1. Prostacyclin.- 4.2. Endothelium-Derived Relaxant Factor.- 5. Oxygen.- 5.1. Hypoxia Vs Anoxia.- 5.2. Oxygen Sensitivity of the Vascular Wall.- 5.3. Oxygen and Release/Transfer of Vasoactive Compounds from Endothelial Cells.- 6. Concluding Remarks.- References.- 11 Role of Cyclic GMP in Endothelium-Dependent Relaxation of Vascular Smooth Muscle.- 1. Introduction.- 2. Elevation of Cyclic GMP Levels in Smooth Muscle by Agents that Act on the Endothelium.- 3. Effects of Inhibitors of Guanylate Cyclase on Endothelium-Dependent Relaxation and Formation of Cyclic GMP.- 3.1. Effects of Free Radical Scavengers and Reducing Agents.- 3.2. Effects of Cyanide.- 4. Effects of Inhibitors of Phosphodiesterase on Endothelium-Dependent Relaxation and Formation of Cyclic GMP.- 5. Effects of Inhibitors of Phospholipase A2, Cyclooxygenase, and Lipoxygenase on Endothelium-Dependent Relaxation and Levels of Cyclic GMP.- 6. Effects of Inhibitors of Na+,K+ Pump and Membrane Depolarizing Agents on Endothelium-Dependent Relaxation and Formation of Cyclic GMP.- 7. Effects of Nitroglycerin-Induced Desensitization on Endothelium-Dependent Relaxation and Formation of Cyclic GMP.- 8. Effects of Contractile Agents on Cyclic GMP Levels and the Role of the Endothelium.- 9. Role of the Endothelium and Cyclic GMP in the Regulation of Basal Tone.- 10. Conclusions.- References.- 12 Modulation by the Endothelium of Agonist-Induced Contractions of Vascular Smooth Muscle.- 1. Introduction.- 2. Modulatory Effect of Endothelium on Agonist-Induced Contractile Responses.- 3. Dependence of Endothelium-Modulated Responses on Calcium.- 4. Calcium Channels and Endothelial Cells.- 5. Possible Importance of Na+-Ca2+ Exchange for Release of EDRF.- 6. Effect of Endothelium on Mobilization of Intracellular Calcium for Contraction.- 7. Effect of Endothelium on Calcium Uptake by Vascular Tissues.- 7.1. Basal Uptake.- 7.2 Stimulated Uptake.- 8. Effect of Endothelium on Efflux of Calcium.- 8.1. Basal Efflux.- 8.2. Efflux of Calcium from Stimulated Tissues.- 9. Effects of Muscarinic Agonists on Ca2+ Influx and Efflux in Vessels With and Without Endothelium.- 10. Importance of the Modulatory Effect of Endothelium on Cellular Ca2+ Movements.- 11. Do Contractile Agonists Stimulate the Release of EDRF or Are Modulatory Effects Dependent on Basal Release of EDRF?.- References.- 13 Endothelium-Derived Relaxing Factor Relaxes Vascular Smooth Muscle by Cyclic GMP-Mediated Effects on Calcium Movements.- 1. Introduction.- 2. Calcium Influx.- 2.1. EDRF.- 2.2. Nitrovasodilators, 8-Bromo-cyclic GMP.- 2.3. Cyclic GMP and Calcium Influx.- 2.4. Specificity for "Receptor-Operated Channels"?.- 3. Calcium Efflux.- 3.1. EDRF.- 3.2. Nitrovasodilators, 8-Bromo-cyclic GMP.- 3.3. Implications of Efflux Data.- 4. Biochemical Mechanisms.- 5. Concluding Remarks.- References.- 14 Heterogeneity in Endothelium-Dependent Relaxations: Acute, Chronic, and Evolutionary Modulations.- 1. Introduction.- 2. Hormones.- 2.1. Acute Effects.- 2.2. Chronic Effects.- 3. Innervation.- 4. Blood Flow.- 4.1. Acute Conditions.- 4.2. Chronic Conditions.- 5. Oxygen.- 5.1. Acute Effects.- 5.2. Chronic Effects.- 6. Concluding Remarks.- References.- 15 Endothelium-Dependent Regulation of Resting Levels of Cyclic GMP and Cyclic AMP and Tension in Pulmonary Arteries and Veins.- 1. Introduction.- 2. Resting Levels of Cyclic GMP and Cyclic AMP.- 3. Endothelium-Dependent Regulation of Vascular Cyclic GMP Levels.- 3.1. Methylene Blue.- 3.2. MB 22948.- 4. Dependence of Activity of EDRF on the Diameter of the Blood Vessels.- 4.1. Artery.- 4.2. Vein.- 5. Relationship Between Resting Cyclic Nucleotide Levels and Endothelial Integrity in Arteries and Veins.- 6. Some Unique Properties of Putative EDRF.- 6.1. Direct Activation of Soluble Guanylate Cyclase.- 6.2. Stability of EDRF..- 6.3. Chemical Reactivity of EDRF.- 6.4. Sites of Action of Agents Affecting EDRF Activity.- 7. Conclusions and Future Direction.- References.- 16 Endothelium-Dependent Responses of Cerebral Arteries.- 1. Introduction.- 2. Endothelium-Dependent Relaxations.- 2.1. Acetylcholine.- 2.2. Bradykinin.- 2.3. Thrombin.- 2.4. Vasopressin and Oxytocin.- 3. Endothelium-Dependent Contractions.- 3.1. Arachidonic Acid, Calcium Ionophore A23187, and Acetylcholine.- 3.2. Anoxia.- 3.3. Potassium.- 3.4. Stretch.- References.- 17 Endothelium, Blood Flow, and Vascular Responses in Large Coronary and Iliac Arteries of the Conscious Dog.- 1. Introduction.- 2. Direct, Endothelium-Independent Vasodilatation.- 3. Endothelium-Mediated, Blood Flow-Independent Vasodilatation.- 4. Endothelium-Dependent, Blood Flow-Mediated Vasodilatation.- 5. Endothelium-Mediated Protection Against Vasoconstriction.- 6. Concluding Remarks.- References.- 18 Endothelium-Dependent Responses in Large Arteries and in the Microcirculation.- 1. Introduction.- 2. EDRF and Reactivity of Large Arteries In Vivo.- 2.1. Sonomicrometry in Femoral and Coronary Arteries under Conditions of Controlled Flow and Pressure.- 2.2. Chronic Measurement of the Diameter of the Carotid Artery after Removal of the Endothelium.- 3. Reactivity of Large Arteries In Vitro.- 3.1. EDRF Is Released by Norepinephrine and Serotonin.- 3.2. Classification of Endothelial Alpha2-Adrenoceptors.- 3.3. Distribution of Alpha2-Adrenoceptors on Endothelium.- 3.4. Comparison of Endothelium-Dependent Agonists in Five Large Arteries.- 3.5. Carotid Artery Reactivity 4 wk after Endothelial Denudation.- 4. Reactivity of Microcirculation to EDRF.- 4.1. Effect of Hypertension on Reactivity of the Hindquarter of the Rabbit.- 4.2. Effect of Cholesterol on EDRF.- 5. EDRF and Coronary Atheroma.- 6. Conclusions.- References.- 19 Endothelium-Dependent Responses in the Peripheral Microcirculation.- 1. Introduction.- 2. Methods.- 2.1. Preparation.- 2.2. X-Ray Techniques. Contrast Medium.- 2.3. Quantitation.- 2.4. Agents Used To Induce Tone. Hemoglobin.- 3. Network Analysis.- 4. Results and Discussion.- 4.1. Basal and Stimulated Release of EDRF. Evidence for a Complex Interaction with Vessel Tone.- 4.2. Regulation of Resistance by Basal EDRF Release.- 4.3. Flow-Dependent EDRF-Mediated Dilatation.- 4.4. Regulation of Flow Distribution by Basal EDRF Release.- 4.5. Influence of Basal EDRF Release on Power Losses and Pressure-Flow Characteristics.- 5. Concluding Remarks.- References.- 20 Endothelium-Dependent Vasodilatation in the Cerebral Microcirculation.- 1. Introduction.- 2. Endothelium-Dependent Vasodilatation from Acetylcholine in Cerebral Microvessels.- 3. Endothelium-Dependent Vasodilatation from Agents Other than Acetylcholine.- 4. Reversibility of Elimination of Endothelium-Dependent Vasodilatation in Cerebral Arterioles.- 5. Nature of EDRF in the Cerebral Microcirculation.- 6. Significance.- References.- 21 Platelets and Endothelium-Dependent Responses.- 1. Introduction.- 2. Platelet-Vessel Interactions.- 2.1. Adhesion.- 2.2. Atherosclerosis.- 3. In Vitro Experiments: Endothelial Response to Platelets.- 3.1. Contractile Responses.- 3.2. Platelet-Induced Relaxations.- 3.3. Serotonin.- 3.4. Adenine Nucleotides.- 3.5. Other Possible Mediators.- 3.6. Other Vessels.- 4. In Vivo Models.- 4.1. Artificial Damage.- 4.2. Atherosclerotic Damage.- 4.3. Coronary Occlusion.- 5. Clinical Studies.- 5.1. Evidence of Platelet Activation.- 5.2. Serotonin.- 5.3. Thromboxane A2.- 6. Conclusions.- References.- 22 Endothelium-Dependent Responses and the Release of Endothelium-Derived Relaxing Factor in Atherosclerotic Blood Vessels.- 1. Introduction.- 2. Atherosclerosis and the Structure of the Blood Vessel Wall.- 2.1. Introduction.- 2.2. The Atherosclerotic Lesions.- 2.3. Mechanism of Atherosclerotic Plaque Formation.- 2.4. Animal Models of Atherosclerosis.- 2.5. Effects of Drugs on the Pathogenesis and Regression of Atherosclerosis.- 3. Vascular Responses in Atherosclerotic Blood Vessels.- 3.1. In Vivo Observations.- 3.2. In Vitro Observations.- 4. Endothelium-Dependent Relaxations in Atherosclerotic Blood Vessels.- 4.1. Introduction.- 4.2. Endothelium-Dependent Relaxations.- 4.3. Endothelium-Independent Relaxations to Nitroglycerin.- 4.4. Effect of Dipyridamole Treatment on Endothelium-Dependent Relaxations in Atherosclerotic Arteries.- 4.5. Release of EDRF.- 5. Conclusions.- References.- 23 Endothelium-Dependent Relaxations in Hypertensive Blood Vessels.- 1. Introduction.- 2. Factors Influencing Vasodilator Responsiveness.- 2.1. Contractile State of Vascular Preparation.- 2.2. Age.- 2.3. Origin of Vasodilator Abnormality.- 3. Relaxations in Hypertensive Blood Vessels.- 3.1. Prior to Discovery of EDRF.- 3.2. Studies Analyzing Endothelium-Dependent Vs Independent Relaxations in Hypertensive Blood Vessels.- 4. Structural and/or Biochemical Endothelial Alterations in Hypertension.- 4.1. Structural Alterations.- 4.2. Biochemical Alterations.- 5. Conclusions.- References.- 24 Mechanisms of Altered Endothelium-Dependent Responses in Hypertensive Blood Vessels.- 1. Introduction.- 2. Morphological Changes.- 3. Endothelium-Dependent Responses in Hypertensive Blood Vessels.- 3.1. Endothelium-Dependent Relaxations.- 3.2. Endothelium-Dependent Contractions.- 3.3. Mechanisms of Altered Endothelium-Dependent Responses in Hypertensive Blood Vessels.- 4. Possible Importance of Altered Endothelial Function in Hypertension.- 4.1. Peripheral Vascular Resistance.- 4.2. Vascular Complications.- 4.3. Antihypertensive Therapy.- References.- 25 Endothelium-Dependent Responses in Human Arteries.- 1. Introduction.- 2. Source Materials and Methods.- 3. Outline.- 4. Response to Acetylcholine.- 5. Other EDRF Releasers.- 6. Inhibitors of EDRF.- 7. "Interesting Negatives".- 8. Concluding Comments.- References.