Adrenergic Activators and Inhibitors

Section I: General Considerations.- 1 Chemistry of Alpha- and Beta-Adrenoceptor Agonists and Antagonists.- A. Introduction.- B. Beta-Adrenergic Agonists.- I. Subclassification of Beta-Adrenoceptors.- II. Structure-Activity Relationships.- 1. Substitution on the Amine Group.- 2. Substitution on the Aromatic Ring.- 3. Side Chain Substitution; Conformation of Phenylethanolamines.- 4. Phenoxypropanolamines.- C. Beta-Adrenergic Antagonists.- I. Potency and Tissue Selectivity.- 1. Side Chain Variations.- 2. Substitution on the Amino Group.- 3. Substitution on the Aromatic Ring.- II. Intrinsic Sympathomimetic Activity.- III. Membrane-Stabilizing Activity.- D. Alpha-Adrenergic Agonists.- E. Subclassification of Alpha-Adrenoceptors.- F. Alpha-Adrenergic Antagonists.- I. Ergot Derivatives.- II. Haloalkylamines; Irreversible Alpha-Blockade.- III. Phenoxyalkylamines and Benzodioxans.- IV. Dibenzazepines and Dibenzazocines.- V. Imidazolines and Related Heterocycles.- VI. Phenylethanolamines.- VII. Piperazines, Piperidines, and Related Heterocycles.- VIII. Yohimbine.- IX. Neuroleptic Drugs.- References.- 2 Sympathomimetic Amine-Induced Responses of Effector Organs Subserved by Alpha-, Beta1-, and Beta2-Adrenoceptors.- A. Introduction.- B. Alpha-Adrenoceptor-Mediated Responses.- I. Vasoconstriction.- II. Spleen Smooth Muscle.- III. Uterus.- IV. Seminal Vesicles.- V. Retractor Penis.- VI. Eye.- VII. Nictitating Membrane.- VIII. Liver.- 1. Glycogenolysis.- 2. Gluconeogenesis.- IX. Intestinal Smooth Muscle.- X. Additional Delineations.- C. Beta1-Adrenoceptor-Mediated Responses.- I. Cardiac Excitation.- II. Cardiac Glycogenolysis.- III. Vascular Smooth Muscle.- 1. Coronaries.- 2. Intestinal Smooth Muscle.- IV. Kidney Renin Release.- V. Adipose Tissue.- 1. White Adipose Tissue Lipolysis.- 2. White Adipose Tissue Lipogenesis.- 3. Brown Adipose Tissue Calorigenesis (Nonshivering Thermogenesis).- VI. Salivary Gland Secretion.- VII. Additional Observations.- D. Beta2-Adrenoceptor-Mediated Responses.- I. Vascular Smooth Muscle Relaxation.- II. Tracheal and Bronchial Smooth Muscle.- 1. Relaxation.- 2. Antianaphylaxis.- III. Skeletal Muscle.- 1. Contraction.- 2. Glycogenolysis (Lacticacidemia).- IV. Potassium Uptake (Hypokalemia).- V. Urinary Bladder.- VI. Uterus.- VII. Insulin Release.- VIII. Gall Bladder.- IX. Vas Deferens.- X. Rat Diaphragm.- XI. Additional Observations.- E. Summary.- References.- 3 Evaluation of Adrenergic Alpha- and Beta-Receptor Activators and Adrenergic Alpha- and Beta-Receptor Blocking Agents.- A. In Vivo Tests.- B. Organ-Perfusion Tests.- C. Isolated Tissues for Evaluation of Adrenergic Drugs.- D. Quantitation of Agonists and Factors Which Affect the Quantitation.- E. Design of an Experiment.- F. Base Line Problems.- G. Analysis of Data.- H. Factors Which Influence the Shapes and Slopes of the Dose-Response Curves of Sympathomimetic Substances.- I. Stereoisomeric Forms.- II. Indirect Action.- III. Density of Adrenergic Innervation.- IV. Distribution of Adrenoceptors.- V. Dose-Response Curves and Ca2+Ions.- VI. Enzymatic Degradation and Drug Disposition.- VII. Miscellaneous Factors.- I. Procedures for Determination of Dissociation Constants (KA) of Agonists.- J. Evaluation of Adrenergic Blockers and Associated Experimental Complications.- K. Evaluation of Adrenergic Drugs in Subcellular Fractions.- L. Concluding Remarks.- References.- 4 Evaluation of Agents That Release or Modify Release of Adrenergic Transmitter.- A. General Considerations.- I. Adrenergic Transmitter-Releasing Agents.- 1. Ganglion Stimulants.- II. Drugs Causing Impaired Transmitter Release.- 1. Major Classes.- 2. The Evaluation of Adrenergic Neurone-Blocking Agents.- 3. The Evaluation of Agents that Deplete Noradrenaline.- 4. Inhibition of Noradrenaline Synthesis.- 5. Evaluation of False Transmitter Substances.- 6. Evaluation of Presynaptic Alpha-Adrenoceptor Agonists.- 7. Other Presynaptic Systems that Reduce Transmitter Release.- B. Some Prefered Methods and Their Use in Evaluating Drugs.- I. Cat Spleen: Release of Adrenergic Transmitter and Motor Responses.- 1. Method.- 2. Evaluation of Drugs.- II. Rabbit Pulmonary Artery: Release of Adrenergic Transmitter and Contractile Response.- 1. Method.- 2. Evaluation of Drugs.- III. Vas Deferens Preparations: Contractions and the Release of Adrenergic Transmitter.- 1. Method.- 2. Evaluation of Drugs.- IV. Perfused Mesenteric Artery of the Rat: Vasoconstrictor Response.- 1. Method.- 2. Evaluation of Drugs.- V. Pithed Rat: Cardiovascular Responses to Sympathetic Activation.- 1. Method.- 2. Evaluation of Drugs.- VI. Anaesthetised Cat: Cardiovascular and Nictitating-Membrane Responses and Reference to Isolated Nictitating-Membrane Preparations.- 1. Methods.- 2. Evaluation of Drugs.- VII. Nictitating-Membrane Relaxation in Unanaesthetised Cats.- VIII. Ptosis in Mice.- IX. Cardiovascular Studies.- 1. Method.- 2. Evaluation of Drugs.- References.- 5 Catecholamine Receptors on Nerve Terminals.- A. Introduction.- B. Prejunctional Alpha-Adrenoceptors on Noradrenergic Nerve Terminals.- I. General Considerations.- II. Effects of Antagonists on Prejunctional Alpha-Adrenoceptors.- 1. Alpha-Adrenoceptor Antagonists and Hypertension.- III. Effects of Agonists on Prejunctional Alpha-Adrenoceptors.- IV. Effects of Partial Agonists on Prejunctional Alpha-Adrenoceptors.- V. Characterization of Prejunctional Alpha-Adrenoceptors.- 1. Localization of Prejunctional Alpha-Adrenoceptors.- 2. Mechanisms of Coupling of Prejunctional Alpha-Adrenoceptors to Inhibition of Transmitter Release.- 3. Differences Between Prejunctional and Postjunctional Alpha-Adrenoceptors.- VI. Inhibitory Feedback Effects of Transmitter on Prejunctional Alpha-Adrenoceptors.- 1. Normal Noradrenergic Transmission.- 2. Effect of Blockade of Transmitter Reuptake.- 3. Effects of Depletion of Noradrenaline Transmitter Stores.- 4. Effect of False Transmitters.- C. Prejunctional Beta-Adrenoceptors on Noradrenergic Nerve Terminals.- I. Effects of Beta-Adrenoceptor Agonists on Noradrenergic Transmission.- II. Effects of Beta-Adrenoceptor Antagonists on Noradrenergic Transmission.- III. A Facilitatory Feedback Loop Through Prejunctional Beta-Adrenoceptors in Noradrenergic Transmission.- 1. Normal Transmission.- 2. Possible Role of Prejunctional Beta-Adrenoceptors in Hypertension.- D. Prejunctional Dopamine Receptors on Noradrenergic Nerve Endings.- I. Possible Relevance of Prejunctional Dopamine Receptors in Understanding Clinical Phenomena.- E. Catecholamine Receptors on Cholinergic Nerve Terminals.- I. Autonomic Cholinergic Nerve Terminals.- 1. Interaction Between Cholinergic and Adrenergic Nerve Terminals.- II. Autonomic Ganglionic Transmission.- 1. Adrenal Medulla.- F. Conclusion.- References.- 6 Adrenergic Agents, Calcium Ions, and Cyclic Nucleotides in the Control of Cell Proliferation.- A. Introduction.- B. Definitions.- C. Proliferative Activation or Modulation by Catecholamines.- I. Salivary Gland Acinar Cells.- II. Squamous Epithelial Cells.- III. Corneal Epithelium, Duodenum, Kidney, and Prostate.- IV. Bone Marrow Precursor (CFU-S) Cells.- V. Thymic Lymphoblasts.- D. Cyclic Nucleotides in Proliferative Development.- I. Proliferative Activation In Vivo.- II. Proliferative Activation In Vitro.- III. Postactivation Phases In Vivo and In Vitro.- E. Calcium in Cell Proliferation.- F. Possible Interaction Mechanism of Calcium and Cyclic AMP in Proliferative Control.- G. Conclusions.- References.- 7 Effects on the Metabolism.- A. Introduction.- B. Carbohydrate Metabolism.- I. Man.- 1. Adrenoceptor Agonists.- 2. Adrenoceptor Antagonists.- II. Baboon and Monkey.- III. Rabbit.- 1. Adrenoceptor Agonists.- 2. Adrenoceptor Antagonists.- IV. Rat.- 1. Alpha-Adrenoceptor Agonists.- V. Mouse.- 1. Adrenoceptor Agonists.- 2. Adrenoceptor Antagonists.- VI. Dog.- 1. Adrenoceptor Agonists.- 2. Adrenoceptor Antagonists.- VII. Cat.- C. Lipid Metabolism.- I. Human.- 1. Adrenoceptor Agonists and Antagonists.- 2. Adipose Tissue In Vitro.- II. Baboon.- III. Rabbit.- 1. Adrenoceptor Agonists.- 2. Adipose Tissue In Vitro.- IV. Rat.- 1. Adrenoceptor Agonists.- 2. Adrenoceptor Antagonists.- 3. Adipose Tissue In Vitro.- V. Mouse.- VI. Dog.- 1. Adrenoceptor Agonists and Antagonists.- 2. Adipose Tissue In Vitro.- VII. Cat.- D. Summary.- References.- Section II: Effects on the Autonomic and on the Central Nervous System.- A. Presynaptic Receptors in the Autonomic Nervous System.- A. Introduction.- B. Early Developments.- C. Effects of Alpha-Adrenoceptor Antagonists.- D. Effects of Adrenoceptor Agonists.- E. Alpha-Receptors on Other Autonomic Nerves and on Adrenal Medullary Cells.- F. The Nature of the Inhibitory Presynaptic Receptor.- G. Mechanism of Alpha-Receptor Mediated Inhibition.- H. Presynaptic Dopamine Receptors.- I. Presynaptic Facilitatory Beta-Receptors.- J. Physiological and Clinical Function of Presynaptic Receptors.- References.- B. Adrenergic Activators and Inhibitors on the Central Nervous System.- 1 Regulation of Monoamine Synthesis and Utilization by Receptors.- A. Introduction.- B. Functional Aspects.- I. Noradrenaline Receptors.- II. Dopamine Receptors.- III. 5-Hydroxytryptamine Receptors.- C. Biochemical Aspects.- I. Noradrenaline.- II. Dopamine.- III. 5-Hydroxytryptamine.- D. Concluding Remarks.- References.- 2 Interactions of Opiates and Endorphins With Cerebral Catecholamines.- A. Introduction.- B. Behavioral Studies.- I. Effects of Pharmacological Manipulation of Central Catecholamines on Opiate Action.- 1. Acute Opiate Effects.- 2. Chronic Opiate Effects.- C. Biochemical Studies.- I. Effects of Opiates on the Content and Turnover of Catecholamines In Vivo.- 1. Acute Opiate Administration.- 2. Chronic Opiate Administration.- 3. Withdrawal.- II. Effects of Opiates on Catecholamine Metabolism In Vitro.- 1. Acute Opiate Administration.- 2. Chronic Opiate Administration.- D. Single Neuron and Receptor Studies.- I. Effects of Opiates on Single Neurons in the Striatum.- II. Interactions Between Opiates and Catecholamine-Blocking Drugs at Opiate and Dopamine Receptors.- E. Catecholamines in Endorphin Mechanisms.- I. Behavioral and Biochemical Studies.- II. Morphological Studies.- F. Summary and Concluding Remarks.- References.- 3 Behavioural Pharmacology Reflecting Catecholamine Neurotransmission.- A. Outlining the Problem.- B. Establishing a Quantitative Relationship Between Neurotransmission and Behaviour.- I. Behavioural Measurements "Amplify Neuronal Degeneration".- II. Matching Neuronal and Behavioural Supersensitivity.- C. Behavioural Patterns Reflect Neurotransmission in Discrete Systems.- D. A New Approach in Behavioural Pharmacology.- E. Where Does Behavioural Pharmacology Fit In - Some Final Reflections.- References.- 4 Regulation of the Arterial Blood Pressure.- A. Introduction.- B. Effects of Centrally Applied Drugs on Arterial Blood Pressure.- I. Brain Stem.- 1. Effects of Adrenoceptor Activators.- 2. Effects of Alpha- and Beta-Adrenoceptor Blocking Drugs.- 3. Effects of Antihypertensive Drugs.- II. Hypothalamus.- 1. Effects of Adrenoceptor Activators.- 2. Effects of Alpha- and Beta-Adrenoceptor Blocking Drugs.- 3. Effects of Antihypertensive Drugs.- C. Catecholamine Mechanisms in Experimental Hypertension.- I. Noradrenaline.- II. Adrenaline.- III. Conclusions.- References.- 5 Catecholamines and the Regulation of Body Temperature.- A. Catecholaminergic Thermogenesis: Peripheral Mechanisms.- B. Central Catecholamines and Heat Dissipation.- I. Action of Norepinephrine on the Hypothalamus.- II. Activity of Endogenous Catecholamines.- III. Dopamine and 6-OH-DA.- C. Drugs Affecting Catecholamine Systems.- I. Alterations in 6-OH-DA Hypothermia.- II. Interference With Catecholamine Synthesis and Degradation.- III. Catecholamine Receptor Mechanisms.- D. Conclusion.- References.- 6 Regulation of Food Intake.- A. Introduction.- B. Brain Norepinephrine and Feeding.- I. Intracerebral Norepinephrine Injections.- II. Pharmacological Considerations.- III. Norepinephrine Neuron Destruction: Acute and Chronic Effects.- IV. Measurements of Norepinephrine Content, Turnover, and Efflux in Relation to Feeding.- C. Brain Dopamine-Containing Neurons and Feeding.- I. Damage to Dopamine-Containing Neurons and the Lateral Hypothalamic Syndrome.- II. Brain Dopamine-Containing Neurons in Experimental Hyperphagias.- 1. Ventromedial Hypothalamic Hyperphagia.- 2. Electrical Brain Stimulation and Tail Pinch.- References.- 7 Regulation of Water Intake.- A. Introduction.- B. Role of Central Catecholamines in Drinking.- I. Lesion Experiments.- II. Central Application of Sympathomimetic Amines and Their Antagonists.- 1. Noradrenaline.- 2. Isoprenaline.- 3. Alpha- and Beta-Receptor Antagonists.- 4. Dopamine and Dopamine Antagonists.- C. Dipsogenic Effects of Catecholamines Administered into the Peripheral Circulation.- D. Conclusion.- References.- Section III: Effects on the Cardiovascular System.- 1 Effect of Adrenergic Activators and Inhibitors on the Electrical Activity of the Heart.- A. Introduction.- B. Cardiac Electrophysiologic Effects and Mechanism of Arrhythmogenic and Antiarrhythmic Actions of Adrenergic Activators.- I. Influence of Activation of Adrenergic Receptors of the Heart on the Electrophysiology of the Cardiac Cell.- II. Ionic Basis of the Mechanism of the Cardiac Electrophysiologic Changes Induced by Activation of Adrenergic Receptors of the Heart.- III. Effects of Activation of Adrenergic Receptors on the Major Electrophysiologic Parameters of the Heart in Situ.- 1. Automaticity.- 2. Conduction, Excitability, and Refractoriness.- IV. Arrhythmogenic Effect of Sympathetic Excitation.- V. Arrhythmogenic Action of Adrenergic Activators.- VI. Morphological Basis of Adrenergically Induced Cardiac Arrhythmias.- VII. Importance of the Adrenergic Beta-Receptors of the Heart in the Arrhythmogenic and Other Cardiac Effects of Adrenergic Activation.- VIII. Adrenergically Induced Cardiac Arrhythmias Due to Reentry Mechanism.- IX. Role of Adrenergic Activation in the Mechanism of Arrhythmias Appearing Under Pathologic Conditions.- 1. Importance of Adrenergic Activation in the Mechanism of Cardiac Arrhythmias Due to Hypothermia.- 2. Possible Mechanism of the Enhanced Susceptibility to Fibrillation of the Hypothermic Heart in Situ.- 3. Significance of Adrenergic Activation in the Mechanism of Cardiac Arrhythmias Due to Generalized Hypoxia.- 4. Role of Adrenergic Mechanisms in the Effect of Regional Myocardial Ischemia on the Susceptibility to Arrhythmia of the Heart.- X. Effect of Adrenergic Activators Other Than Natural Catecholamines on Cardiac Electrophysiologic Properties.- C. Cardiac Electrophysiologic Effects and the Mechanism of Antiarrhythmic Action of Adrenergic Inhibitors.- I. Effect on Cardiac Electrical Activity and Antiarrhythmic Properties of Adrenergic Receptor Blocking Substances.- 1. Effect of Adrenergic Alpha-Receptor Blocking Agents on the Electrical Activity and Dysrhythmias of the Heart.- 2. Effect of Adrenergic Beta-Receptor Blocking Substances on Cardiac Electrophysiology at the Cellular Level as Well as in Heart in Situ.- II. Effect of Adrenergic Nerve-Ending Inhibitors and Neural Transmitter Depleting Agents on Some Electrophysiologic Properties of the Heart and Their Mode of Action in Cardiac Arrhythmias.- References.- 2 Effects of Beta- and Alpha-Adrenoceptor Activators and Adrenergic Transmitter Releasing Agents on the Mechanical Activity of the Heart.- A. Introduction.- B. Effects of Beta-Adrenoceptor Activators.- I. Characterization of the Beta-Adrenergic-Mechanical Response.- 1. Time Course of the Beta-Adrenergic Positive Inotropic Effect.- 2. Mechanical Characteristics of Beta-Adrenergic Inotropism.- 3. Calcium Dependence of the Beta-Adrenergic Inotropic Response.- 4. Sodium Dependence of the Beta-Adrenergic Inotropic Response.- 5. Potassium Dependence of the Beta-Adrenergic Inotropic Response.- 6. Temperature Dependence of the Beta-Adrenergic Inotropic Response.- 7. Influence of Acid-Base Changes on the Beta-Adrenergic Inotropic Response.- 8. Frequency Dependence of the Beta-Adrenergic Inotropic Response.- 9. Effects of Beta-Adrenergic Agonists on Rested-State Contractions.- 10. Effects of Beta-Adrenergic Agonists on Potassium Contractures.- 11. Summary of the Characteristics of the Beta-Adrenergic Mechanical Response.- II. Possible Mechanism(s) of the Positive Inotropic and Relaxant Effects of Beta-Adrenergic Stimulation.- 1. Effects of Beta-Adrenergic Stimulation on Myocardial Calcium Movements.- 2. Beta-Adrenergic Mechanical Effects and C-AMP.- 3. Possible Mechanisms and Sites of Regulatory Effects of C-AMP.- 4. Mechanical Effects of Beta-Adrenergic Stimulation and C-GMP.- 5. Summary of the Possible Mechanism(s) of the Positive Inotropic and Relaxant Effects of Beta-Adrenergic Stimulation.- C. Effects of Alpha-Adrenoceptor Activators.- I. Do Alpha-Adrenoceptors Mediating Mechanical Responses Exist in Cardiac Muscle?.- II. Mechanical Effects of Phenylephrine.- 1. Characterization of the Adrenoceptors Mediating the Positive Inotropic Effect of Phenylephrine.- 2. Time Course of the Positive Inotropic Effect of Phenylephrine.- 3. Mechanical Characteristics of the Positive Inotropic Effect of Phenylephrine and Effect on Potassium Contractures.- 4. Frequency Dependence of the Positive Inotropic Effect of Phenylephrine.- 5. Temperature Dependence of the Positive Inotropic Effect of Phenylephrine.- 6. Dependence of the Positive Inotropic Effect of Phenylephrine on Thyroid Hormone.- 7. Positive Chronotropic Effect of Phenylephrine.- III. Positive Inotropic Effects of Methoxamine and Other Alpha-Sympathomimetic Agents.- IV. Possible Mechanism(s) of the Positive Inotropic Effect of Alpha-Adrenergic Stimulation.- 1. Effects of Alpha-Adrenergic Stimulation on Myocardial Calcium Movements.- 2. Alpha-Adrenergic Positive Inotropic Effects and C-AMP.- 3. Alpha-Adrenergic Positive Inotropic Effects and C-GMP.- V. Summary and Conclusions on the Mechanical Effects of Alpha-Adrenergic Stimulation.- D. Effects of Adrenergic Transmitter Releasing Agents.- E. Concluding Remarks.- References.- 3 Effects of Adrenergic Activators and Inhibitors on the Coronary Circulation.- A. Introduction.- B. Effects of Adrenaline and Noradrenaline on Coronary Blood Flow.- I. Evidence Supporting Vasoconstriction as the Primary Effect of Noradrenaline on Coronary Vessels.- 1. Experiments Involving Cardiac Sympathetic Nerve Stimulation.- 2. Local and/or Systemic Administration of Noradrenaline in Conscious Animals.- 3. Effects of Adrenaline and Noradrenaline in Anaesthetized Animals, Especially After Beta-Adrenoceptor Blockade.- 4. Experiments on Isolated Heart Preparations.- 5. Effects of Noradrenaline and Adrenaline on Isolated Coronary Vessels.- II. Evidence Supporting Vasodilatation as the Primary Effect of Noradrenaline and Adrenaline on Coronary Vessels.- 1. Experiments in Conscious Animals.- 2. Experiments in Anaesthetized Animals.- 3. Isolated Coronary Perfused or Nonworking Heart Preparations.- 4. Isolated Coronary Vessels.- III. Effects of Noradrenaline in Myocardial Ischaemia.- C. Coronary Responses to Other Beta-Adrenoceptor Stimulating Drugs.- I. Isoprenaline.- 1. General Effects.- 2. Effects on the Distribution of Blood Flow in the Left Ventricular Wall.- 3. Effects in Acute Myocardial Ischaemia.- II. Salbutamol.- III. Oxyfedrine.- 1. General Effects.- 2. Effects in Acute Myocardial Ischaemia.- IV. Dopamine.- 1. General Effects.- 2. Effects in Acute Myocardial Ischaemia.- V. Dobutamine.- 1. General Effects.- 2. Effects in Acute Myocardial Ischaemia.- VI. Miscellaneous Drugs.- D. Effects of Beta-Adrenoceptor Blocking Drugs on Coronary Blood Flow.- I. Dichloroisoprenaline.- II. Pronethalol.- III. Propranolol.- 1. Effects in Anaesthetized Animals.- 2. Possible Mechanisms for the Reduction of Blood Flow.- 3. Effects on the Distribution of Blood Flow Across the Left Ventricular Wall.- 4. Effects in Conscious Dogs and Monkeys.- 5. Effects on Coronary Blood Flow in Man.- 6. Effects in Acute Myocardial Ischaemia.- IV. Practolol.- 1. General Effects.- 2. Effects in Acute Myocardial Ischaemia.- 3. Use in Analysing the Coronary Vascular Beta-Adrenoceptor Type.- V. Oxprenolol.- VI. Sotalol.- VII. Alprenolol.- VIII. Pindolol.- IX. Timolol.- X. Tolamolol.- XI. Atenolol.- XII. Labetalol.- E. Drugs With Predominantly Alpha-Adrenoceptor Activity and Drugs Acting Indirectly by Release of Neuronal Noradrenaline.- I. General Effects.- II. Effect of Alpha-Adrenoceptor Agonists in Acute Myocardial Ischaemia.- F. Effects of Alpha-Adrenoceptor Blocking Agents on Coronary Blood Flow.- G. Adrenergic Neurone Blockade and the Coronary Circulation.- References.- 4 Effects on Myocardial Metabolism.- A. Action of Adrenergic Agonists.- I. General Aspects.- 1. Introduction.- 2. Mode of Action.- II. Metabolic Actions of Adrenergic Agonists.- 1. Glycogenolysis/Glycolysis.- 2. Lipolysis.- 3. Adenine Nucleotides.- 4. Development of Cardiac Hypertrophy.- B. Action of Adrenergic Antagonists.- I. Beta-Blocking Agents.- II. Alpha-Blocking Agents.- C. Endogenous Neurotransmitter Depleting and Releasing Agents.- References.- 5 Effects on the General Hemodynamics and Peripheral Circulation.- A. Adrenergic Activators.- I. Introduction.- 1. Historical Aspects.- 2. Division of Vasculature.- II. Adrenaline (Epinephrine).- 1. General Hemodynamics.- 2. Cerebral Circulation.- 3. Renal Circulation.- 4. Splanchnic Circulation.- 5. Circulation of Skeletal Muscles and Skin.- III. Noradrenaline (Norepinephrine).- 1. General Hemodynamics.- 2. Cerebral Circulation.- 3. Renal Circulation.- 4. Splanchnic Circulation.- 5. Circulation of Skeletal Muscles and Skin.- IV. Dopamine.- 1. General Hemodynamics.- 2. Cerebral Circulation.- 3. Renal Circulation.- 4. Splanchnic Circulation.- 5. Circulation of Skeletal Muscles.- 6. Aorta.- V. Isoprenaline.- 1. General Hemodynamics.- 2. Cerebral Circulation.- 3. Renal Circulation.- 4. Splanchnic Circulation.- 5. Circulation of Skeletal Muscles and Skin.- VI. Phenylephrine.- VII. Mephentermine.- VIII. Metaraminol.- IX. Methoxamine.- X. Tyramine.- XI. Amphetamine.- XII. Ephedrine.- XIII. Dobutamine.- XIV. L-Dopa.- XV. Clonidine.- XVI. Effects of Adrenergic Activators on Veins.- B. Adrenergic Alpha-Receptor Blocking Agents.- I. Introduction.- II. Hemodynamic Effects of Acute Administration.- 1. General Hemodynamics.- 2. Cerebral Circulation.- 3. Renal Circulation.- 4. Splanchnic Circulation.- 5. Circulation of Skeletal Muscles and Skin.- 6. Pulmonary Circulation.- 7. Veins.- III. Effects of Alpha-Adrenergic Blocking Drugs on Pressor Responses to Various Adrenergic Agonists and Reflectory Stimuli.- IV. Use of Adrenergic Alpha-Receptor Blocking Agents in Cardiovascular Therapeutics.- C. Adrenergic Beta-Receptor Blocking Agents.- I. Hemodynamic Effects of Acute Administration.- II. Hemodynamic Effects of Subacute and Prolonged Administration in Animals.- III. Hemodynamic Effects of Prolonged Administration in Man.- 1. General Considerations.- 2. Hemodynamic Effects of the Antihypertensive Treatment With Adrenergic Beta-Receptor Blocking Agents.- D. Reserpine.- I. Introduction.- II. Hemodynamic Effects of Acute Administration.- 1. Animals.- 2. Man.- III. Effects on Vasomotor Reflexes.- IV. Effects on Responses to Various Vasoactive Agents.- V. Hemodynamic Effects of Subacute Administration.- VI. Hemodynamic Effects of Chronic Administration.- 1. Animals.- 2. Man.- E. Adrenergic Neuron Blocking Agents.- I. Hemodynamic Effects of Acute Administration.- II. Hemodynamic Effects of Prolonged Administration in Animals.- III. Hemodynamic Effects of Subacute and Prolonged Administration in Man.- F. Methyldopa.- I. Hemodynamic Effects in Animals.- II. Hemodynamic Effects in Man.- References.- Author Index.