Angiotensin

ISBN-13: 9783642656026 / Angielski / Miękka / 2011 / 594 str.

I.H. Page;F.M. Bumpus

Opis

The history of arterial hypertension is both long and short; long, since BRIGHT (1827) first related hardness of the pulse to hardness of the kidneys and hyper. trophy of the heart; short in that modern research began in the late twenties. Most of what we know of these diseases has been discovered in the past fifty years. The modern story should have begun in 1897 when an extract of kidney was shown to be pressor. But little was done with knowledge until about 1929 when the relationship of this kidney extract called "renin" to hypertension was pos- tulated. The pressor effects were, however, unlike most of those seen with sub- stances such as epinephrine or vasopressin. Plasma was required for action of renin and the active substance appeared to be protein. In 1939, it was shown that renin was not in itself a pressor substance but rather a proteolytic enzyme which produced a powerful pressor substance acting on a substrate synthesized by the liver. Later it was noted that the first definable step after the formation of this peptide was cleaving of the decapeptide which had little or no demonstrable activity, with loss of two amino acids to form the octapeptide called "angiotensin." Within a decade synthesis was achieved which made the substance available for world-wide study.

Spis treści

The Biological Production of Angiotensin.- Renin Substrate.- Assay.- Distribution.- Formation.- Factors Affecting Plasma Levels.- Purification and Properties of Hog Substrate.- Structure of the Tetradecapeptide Substrate.- Human Substrate.- Substrate from Other Species.- Other Sources of Angiotensin.- Renin.- Distribution.- Purification and Properties of Animal Renins.- Purification and Properties of Human Renin.- Pseudorenin.- Modified Renin.- Modifiers of the Renin Reaction.- Conclusion.- References.- The Fate of Angiotensin I.- Methods for Measuring Conversion.- Conversion of Angiotensin I in Plasma and Blood.- Conversion of Angiotensin I in Tissues.- a) Lung.- b) Peripheral Vascular Beds.- 1. Hindquarters.- 2. Intestine.- 3. Adrenal Gland.- 4. Kidney.- Intra-Renal Role of the Renin-Angiotensin System.- Summary.- References.- Converting Enzyme in Yitro Measurement and Properties.- Assay Methods.- 1. Methods Using Angiotensin I as Substrate.- a) Biological Methods.- b) Physicochemical Methods for Assay of CE.- c) Discussion.- 2. Methods Using Short Substrates.- a) Physicochemical Methods.- b) Discussion.- 3. Summary of Assay Methods.- Sources of Converting Enzyme.- 1. Blood.- 2. Lung.- 3. Other Tissues.- Methods of Preparation.- 1. Blood.- 2. Lung.- Properties of Converting Enzymes.- 1. Molecular Weight.- 2. Temperature and pH Stability.- 3. pH-Dependence of Activity.- 4. Substrate Specificity.- 5. Effect of Anions.- 6. Effect of Cations.- 7. Inhibitors.- a) Non-Peptide Inhibitors.- b) Peptide Inhibitors.- 8. General Comparison of CE Activities.- 9. Converting Enzyme and Bradykininase.- Atypical Converting Enzyme.- 1. Bacterial Enzymes.- 2. Mammalian Enzymes.- Pathological Factors Affecting Converting-Enzyme Activity in Vitro.- 1. Liver Damage.- 2. Hypertension.- References.- The Fate of Angiotensin II.- I. Introduction.- II. Technical Aspects.- A. The Problem of Lower Homologs.- B. The Problem of Labelled Analogs.- 1. Specific Activity.- 2. Random Tritiation.- 3. Labelling During Synthesis.- 4. Labelling by Catalytic Hydrogenation.- C. Strategies for Identifying Metabolites.- III. Mechanisms by Which Angiotensin II is Removed from the Circulation.- A. Binding at Sites of Action.- B. Enzymic Degradation.- 1. Enzymes of Blood.- 2. Angiotensinase Enzymes of Disrupted Solid Tissues.- 3. Angiotensinase Enzymes in Various Vascular Beds.- C. Elimination by Binding.- D. Elimination by Synthetic Reactions.- E. Cellular Uptake and Transfer to Extracellular Spaces.- References.- Catabolism of Angiotensin II.- Catabolism of Angiotensin II.- Nature of Angiotensinases.- Angiotensinases in Plasma, Serum, and Blood.- Kidney Angiotensinases.- Liver Angiotensinases.- Lung Angiotensinases.- Cardiac Angiotensinases.- Hind Quarter Angiotensinases.- Changes in Angiotensinase Acticity in Various States.- Changes in Plasma and Serum.- Effects of Changes in Sodium Balance and Other Conditions on Angiotensin-II Catabolism.- Angiotensinase Assays.- Summary.- References.- Structure-Activity Relationship in Angiotensin II Analogs.- Pressor and Myotropic Response.- Synthesis of Analogs of Angiotensin II as Specific Antagonists of the Parent Hormone.- Conformation of Angiotensin II.- References.- Antagonists of Angiotensin II.- I. Antagonists Blocking the Indirect Actions.- II. Drugs Which Antagonize Direct Effects of Angiotensin.- A. Physiologic (Indirect) Antagonists.- B. Direct Pharmacological Antagonists of Angiotensin.- 1. Non-Competitive Antagonists.- 2. Competitive Antagonists of Angiotensin.- Summary.- References.- Tachyphylaxis to Angiotensin.- A. Characteristics of Tachyphylaxis.- 1. Dose and Time Dependence.- 2. Drug Specificity.- 3. Species and Tissue Specificity.- B. Occurrence of Tachyphylaxis to Angiotensin.- C. Mechanism of Tachyphylaxis.- 1. Possible Mechanisms for Production of Tachyphylaxis.- 2. Receptor Saturation and Agonist Destruction.- 3. Receptor Modification as a Mechanism for Tachyphylaxis Production.- 4. Transmitter Exhaustion and Tachyphylaxis.- 5. A Suggested Mechanism for Angiotensin Tachyphylaxis in Smooth Muscle.- References.- Immunogenicity and Antigenicity ol Angiotensin I and II.- Immunogenicity of Angiotensin I and II.- Antigenicity of Angiotensin I and II and their Analogues.- Discussion and Conclusion.- References.- Measurement of Renin and of Angiotensin (Extraction and Bioassay).- I. Angiotensin.- II. Methods for Measurement of “Renin”.- a) Methods Proposed for Measurement of Plasma Renin Activity.- b) Plasma Renin Concentration (PRC).- c) Other Methods.- Discussion and Conclusion.- References.- Angiotensin Immunoassay.- Development of Antibodies to Angiotensin.- Labelled Angiotensin.- Angiotensin Standards.- The Standard Angiotensin Immunoassay Curve.- Angiotensin II: Immunoassay of Levels in Circulating Blood.- Estimation of Angiotensin II — Levels in Other Body Fluids.- Application of Angiotensin Immunoassay to the Measurement of Plasma Renin Activity.- 1. Angiotensin I Immunoassay.- 2. Angiotensin II Immunoassay in the Estimation of Renin Activity.- Other Renin Assays.- Angiotensin II Levels and Plasma Renin Activity in Various States.- Plasma Angiotensin II.- Plasma Angiotensin I Generation Rate in vitro (Plasma Renin Activity).- Renin-Angiotensin II Correlations.- Angiotensin I Levels in Human Plasma.- Conclusion.- References.- Bioassay of Angiotensin.- Methods of Measuring Rat Blood Pressure.- Isolated Organ Techniques.- Continuously Superfused, Blood-Bathed Organ Techniques.- Methods.- Limitations of the Methods.- Calculation of Assay Results.- Pressor Assay.- Myotropic Assay.- General Information on Programs.- Adrenal Medulla.- References.- Plasma of Serum Vasopressor Peptides Other than Angiotensins.- A. Peptides Formed by the Action of Pepsin.- I. Pepsitensin.- II. Oxytocic Peptide: Pepsitocin.- III. Antidiuretic Peptide: Pepsanurin.- B. Vasopressor Peptides Formed by the Action of Proteolytic Enzymes Other than Pepsin.- I. Effect of Proteinase in Alpha-Amylase Preparation.- II. Effect of Chymotrypsin.- C. Vasopressor Peptides Formed in Plasma or Serum by Acidification.- D. Vasopressor Albumin (VA) Formed in Plasma or Serum Incubated at 37°C at Normal pH for Several Hours (5–96) under Sterile Conditions.- E. Other Unidentified Components of Plasma with Vasopressor Activity.- References.- Primary Aldosteronism: Importance of the Level of Plasma Benin as an Adjunct in Diagnosis.- Background.- Methods which have been Employed for Estimating Renin Concentration in Primary Aldosteronism.- Hypokalemic Primary Aldosteronism.- Normokalemic Primary Aldosteronism.- “Idiopathic” Aldosteronism.- Low Renin in Essential Hypertension.- Comment.- References.- Secondary Hyperaldosteronism.- Abnormalities of the Renin-Angiotensin System.- Hypertension.- Malignant Hypertension.- Essential Hypertension.- Renal Hypertension.- Indeterminate Hyperaldosteronism.- Renin-Secreting Tumor.- Hypertension not Present.- Bartter’s Syndrome.- Renal Disorders.- Pregnancy.- Estrogen Treatment.- Abnormalities of ACTH Secretion.- Abnormalities of Potassium Metabolism.- References.- Intermediary Metabolism of Aldosterone.- A. Biogenesis of Aldosterone.- 1. Functional Zonation of the Adrenal Cortex: Aldosterone Secretion by the Zona Glomerulosa.- 2. Aldosterone Biosynthetic Sequence.- 3. Alternative Pathways of Aldosterone Biosynthesis.- 4. Activation of Aldosterone Biosynthesis.- a) Angiotensin II.- b) ACTH.- c) Cyclic AMP.- d) Prostaglandins.- e) Potassium and other Monovalent Cations.- f) NADPH.- g) Serotonin.- B. Distribution and Metabolic Fate of Aldosterone.- C. The Biotransformation and Disposal of Aldosterone.- 1. Aldosterone-18-Glucuronide.- 2. Tetrahydroaldosterone.- D. Quantitative Aspects of the Intermediary Metabolism of Aldosterone.- 1. The Measurement of Aldosterone in Plasma.- 2. Urinary Aldosterone Metabolite Excretion per 24 h.- a) Measurement of Aldosterone-18-Glucuronide Excretion.- b) Urinary Tetrahydroaldosterone-3-Glucuronide.- 3. Determination of the Aldosterone Secretion Rate for a 24-h Period.- References.- The Renin-Angiotensin System in the Control of Aldosterone Secretion.- Evidence for an Aldosterone-Stimulating Hormone in the Control of Aldosterone Secretion.- Early Evidence on the Relation of the Kidney and Adrenal Cortex.- Discovery of the Renin-Angiotensin-Aldosterone System.- Evidence for the Renin-Angiotensin-System as a Primary Mechanism in the Control of Aldosterone Secretion.- 1. Pattern of Steroid Response to Angiotensin II.- 2. Direct Action of Angiotensin II on Adrenal Cortex.- 3. Effects of Nephrectomy and Saline Extracts of Kidneys in Experimental Secondary Aldosteronism.- 4. Effects of Prolonged Infusion of Angiotensin II.- 5. Evidence from Renal Renin Content, JG Cells and the Pressor Response to Angiotensin II.- 6. Effects of Antibodies to Renin Preparations on Aldosterone Secretion and Sodium Excretion.- 7. Plasma Renin Activity and Plasma Angiotensin II in Secondary Aldosteronism.- 8. Comparative Physiology of the Renin-Angiotensin-Aldosterone System.- A Negative Feedback Mechanism in the Control of Aldosterone Secretion.- The Renin-Angiotensin System in Various Types of Secondary Aldosteronism.- 1. Hemorrhage.- 2. Thoracic Caval Constriction.- 3. Congestive Heart Failure.- Summary and Conclusions.- References.- Aldosterone Regulation in Sodium Deficiency: Role of Ionic Factors and Angiotensin II.- A. Format.- B. Introduction.- C. Factors with Direct Action on Aldosterone Secretion.- 1. ACTH.- 2. Potassium.- 3. Renin-Angiotensin II.- 4. Sodium.- D. Interaction between Factors and Alteration of Adrenal Sensitivity.- E. Time Course of Action on Aldosterone Biosynthesis.- F. Biosynthetic Model.- G. Aldosterone Secretion in Response to Sodium Depletion.- H. The Renin-Angiotensin System.- J. Central Nervous Mechanisms Affecting Aldosterone Regulation.- K. Summary of Aldosterone Regulation in Sodium Deficiency.- References.- Effects of Aldosterone on Blood Pressure, Water, and Electrolytes.- Pharmacokinetics of Aldosterone.- Aldosterone and Blood-Pressure Regulation.- Blood-Pressure Raising Effect of Aldosterone and Other Mineralocorticoids.- Eclampsia-Like Syndrome.- Metacorticoid Hypertension.- Adrenal Regeneration Hypertension.- Effects of Hypertension on the Production and Secretion of Aldosterone.- Effects of Aldosterone on Electrolytes.- Chronic Effects of Aldosterone on Electrolytes.- Electrolyte Balance Studies.- Mechanism of Renal Sodium Escape.- The Renin-Angiotensin System and Sodium Escape.- Effect of Aldosterone on Calcium and Magnesium Balances.- Mechanism of Aldosterone Action on Electrolyte Transport.- Effect of Aldosterone on ATPase Activity.- Summary.- References.- Adrenal Medulla.- References.- Central Neurogenic Effects of Angiotensin.- Site of Action of Angiotensin in the Brain Stem.- Additional Sites of Action of Angiotensin in the Brain.- Hemodynamic Features of the Pressor Response to Administration of Angiotensin via the Vertebral Arteries.- Mode of Action of Angiotensin on the Brain Stem.- Summary.- References.- Peripheral Effects of Angiotensin on the Autonomic Nervous System.- Parasympathetic Nervous System and Sympathetic Ganglia.- Cardiac Innervation.- Innervation of Peripheral Vasculature.- Production of Hypertension Through an Action on the Sympathetic Nervous System.- References.- Angiotensin on Vascular Smooth Muscle.- Direct and Indirect Action.- Tachyphylaxis and Autopotentiation.- Angiotensin Receptors.- Heterogeneity of Vascular Smooth Muscle in Its Responsiveness to Angiotensin.- Interventions that Alter the Angiotensin Response.- Electrolytes and the Mechanism of the Contractile Response to Angiotensin.- Summary.- References.- Circulatory Effects of Angiotensin.- I. Effects on the Heart.- A. Myocardial Contractility.- B. Heart Rate.- C. Cardiac Output.- II. Effects on Regional Blood Flow.- A. Coronary Circulation.- B. Pulmonary Circulation.- C. Splanchnic Circulation.- D. Cerebral Circulation.- E. Other Vascular Beds.- III. Effects on Systemic Circulation.- A. Venous System.- B. Arterial Pressure.- References.- Effects of Angiotensin on the Renal Circulation.- I. General Effects of Angiotensin on Renal Hemodynamics.- II. Effects of Small Doses on Renal Blood Flow, Glomerular Filtration Rate and Urine Flow.- 1. Effects of Intravenous Infusions.- 2. Effects of Intra-Arterial Infusion of Angiotensin I and II.- 3. Effect of Angiotensin on Renal Autoregulation.- III. Factors Modifying Renal Response to Angiotensin.- 1. Effect of Anesthesia.- 2. Role of the Autonomic Nerves.- 3. Effect of Dose on Sustained Vascular Response.- 4. Interrelationships between Arterial Pressure, Pressor Responses to Angiotensin and Renal Responses to Angiotensin.- IV. Influence of the Level of Salt Intake on Renal Responses to Angiotensin.- V. Natriuretic Effects of High Doses of Angiotensin.- 1. Time Related Nature of Diuretic Response.- 2. Factors Influencing Diuretic Responses to Angiotensin.- 3. Direct Evidence of the Tubular Effect of Angiotensin.- VI. Angiotensin Effects on Isolated Tissues.- VII. Alterations in Intrarenal Hemodynamics with Angiotensin.- 1. Comparative Effects of Angiotensin on Renal and Other Vascular Beds….- 2. Changes in Segmental Renal Vascular Resistance.- 3. Changes in Regional Intrarenal Vascular Resistance and Intrarenal Distribution of Renal Blood Flow.- VIII. Effect of Sodium Balance, Renin Content of the Kidneys, Pregnancy, Hypertension, and Cirrhosis on the Renal Response to Angiotensin.- 1. Sodium Balance.- 2. Renal Artery Stenosis.- 3. Hypertensive Patients.- 4. Hepatic Cirrhosis.- 5. Pregnancy.- IX. Resume.- References.- Intrarenal Action of Angiotensin.- Location of the Enzymes of the Renin-Angiotensin System in the Kidney.- Intrarenal Formation of Angiotensin II.- The Action of Angiotensin on Tubular Resorption of Sodium.- Angiotensin: Its Role in the Tubulo-Glomerular Feedback Mechanism.- References.- Morphological Effects of Angiotensin on Arteries.- Vessel Changes.- A. Aorta and Major Branches.- B. Small Arteries.- 1. Mesentery and Intestine.- 2. Renal Vessels.- 3. Rabbit Ear Chamber.- C. Afferent Arterioles and Juxtaglomerular Apparatus.- Pathogenesis of Hypertensive Vascular Damage.- A. Role of Angiotensin.- B. Mechanical Factors.- 1. Distension.- 2. Vascular Dynamics.- 3. Hypertension.- Summary.- References.- Effects of Angiotensin II on the Permeability of the Vascular Wall.- Endothelial Cell Contraction.- Effects of Angiotensin II in Other Vascular Cells.- Role of Platelets.- References.- Biochemical Effects of Angiotensin.- I. Effects on Intact Organisms.- II. Effects in Vitro.- A. Effects on Intact Tissues.- B. Effects on Subcellular Fractions.- 1. Receptors.- 2. Microsomes.- C. Mitochondria.- D. Effects on Miscellaneous Chemicals.- Discussion.- References.- Some Possible Functions of Angiotensin.- Author Index.