The protective arm of the renin angiotensin system : functional aspects and therapeutic implications / Thomas Unger, Ulrike M. Steckelings, Robson A.S. dos Santos.

Format:

Book

Author/Creator:

Unger, Th., author.

Steckelings, Ulrike M., author.

Santos, Robson A. S. dos (Robson Augusto Souza dos), author.

Language:

English

Subjects (All):

Renin-angiotensin system.

Physical Description:

1 online resource (312 pages) : illustrations

Edition:

1st ed.

Place of Publication:

Amsterdam, [Netherlands] : Academic Press, 2015.

Summary:

The Protective Arm of the Renin Angiotensin System: Functional Aspects and Therapeutic Implications is the first comprehensive publication to signal the protective role of a distinct part of the renin-angiotensin system (RAS), providing readers with early insight into a complex system which will become of major medical importance in the near.

Contents:

Front Cover

The Protective Arm of the Renin-Angiotensin System: Functional Aspects and Therapeutic Implications

Copyright

Contents

Contributors

Chapter 1: The Angiotensin AT 2 Receptor: From Enigma to Therapeutic Target

Introduction

References

Chapter 2: The AT 2 Receptor: Historical Perspective

Background to the Early Involvement of Ciba-Geigy in the Angiotensin Field

Two Ang II Receptor Subtypes

Angiotensin II Receptor Nomenclature

Early Research on the Role of the AT 2 Receptor

Conclusion

Chapter 3: Animal Models with a Genetic Alteration of AT 2 Expression

Blood Pressure

Cardiac Disease

Vascular Disease

Renal Disease

Neural Disease

Chapter 4: AT 2 Receptor Signaling: Solved and Unsolved

AT 2 R Dimerization

Proliferation and Differentiation

Apoptosis

Inflammation

Fibrosis

Solved and Unsolved Issues

Chapter 5: AT 1 R - AT 2 R Cross Talk

Cross Regulation of Angiotensin II Type 1 Receptor and the Angiotensin II Type 2 Receptor

Functional Significance of the AT 1 R - AT 2 R Cross Talk

Chapter 6: The Angiotensin AT 2 Receptor in Myocardial Infarction

AT 2 Receptor Expression in the Heart

Acute-Phase Postmyocardial Infarction

Cardiac Function

Bradykinin/Nitric Oxide System

Intracellular Acidosis

Tissue Regeneration

Late-Phase Postmyocardial Infarction

Cardiac Fibrosis

Cardiac Hypertrophy

Extracellular Matrix Degradation

Chapter 7: AT 2 R, Vascular Effects, and Blood Pressure

AT 2 Vasorelaxation: In Vitro Preclinical Studies

Acute AT 2 R Vasodilatation/ BP Effects: In Vivo Preclinical Studies.

Chronic AT 2 R Effects on BP: Preclinical Studies

Human Vascular AT 2 R Function: Ex Vivo and In Vivo Studies

AT 2 R Vasorelaxation: Why Is There no Translation into Antihypertensive Effects in Chronic Studies?

Acknowledgments

Chapter 8: AT 2 R in Nervous System

AT 2 R Expression in CNS

AT 2 R Expression in Neuronal Injury

AT 2 R -Mediated Effects in CNS Cells

AT 2 R in Peripheral Neuronal Injury

AT 2 R Stimulation in Stroke

AT 2 R in Spinal Cord Injury

AT 2 R in Multiple Sclerosis

AT 2 R in Traumatic Brain Injury

Chapter 9: Roles of AT 2 R in Cognitive Function

Preventive Effects of ARB on Cognitive Decline and Dementia

Protection Against Ischemic Brain Damage by AT 2 R Stimulation

Role of AT 2 R Stimulation in Cognitive Function

Role of AT 2 R-Associated Proteins in Cognitive Function

Chapter 10: The Protective Role of Angiotensin II ( AT 2) Receptors in Renal Disease: Molecular Mechanisms and Indications ...

Renal AT 2 R Expression

Findings from AT 2 R Knockout ( AT 2 KO) Mice

AT 2 R -Mediated Signaling Pathways

Renoprotective Mechanisms of AT 2 R Stimulation

Inflammation and Oxidative Stress

Fibrosis and Extracellular Matrix Accumulation

AT 2 R -Mediated Modulation of Other RAS Components

Additional Mechanisms Involved in AT 2 R -Mediated Renoprotection

AT 2 R in Renal Disease Associated with Obesity/Diabetes

Chapter 11: AT 2 Receptors and Natriuresis

Renal Expression of AT 2 Rs

AT 2 R Induction of Natriuresis: Initial Evidence

Role of Angiotensin III in AT 2 R -Induced Natriuresis

Nephron Sites and Mechanisms of AT 2 R -Induced Natriuresis via ANG III.

AT 2 R -Dopamine D 1 -Like Receptor Interactions

Physiological Significance of Renal AT 2 Rs in Renal Na + Excretion

AT 2 R -Induced Natriuresis in Disease States

AT 2 R Agonist Administration and Natriuresis

Chapter 12: The Role of the AT 2 R in Vascular Remodeling

The Theoretical Concept of the Role of AT 2 R in Vascular Remodeling

AT 2 R and Hypertension-Induced Vascular Remodeling

AT 2 R and Atherosclerosis

AT 2 R and Aortic Aneurysm

Chapter 13: The AT 2 Receptor and Inflammation

AT 2 R Signaling in Inflammation

Inflammation in Cardiovascular Disease and the Role of the AT 2 Receptor

Atherosclerosis

Myocardial Infarction: Heart Failure

Stroke

Renal Injury

Inflammation in Autoimmune Disease and the Role of the AT 2 Receptor

Conclusions

Chapter 14: The AT 2 Receptor and Interacting Proteins (ATIPs) in Cancer

The Renin-Angiotensin System and Cancer

The AT 2 Receptor and Cancer

AT 2 Receptor-Interacting Proteins (ATIPs) and Cancer

Chapter 15: AT 2 R and Sympathetic Outflow

AT 2 R Ontogeny in Rodent Brain

Effect of AT 2 R Activation on Neuronal Electrophysiological Characteristics

AT 2 R and Sympathetic Regulation in Normal States

Effects of the AT 2 R on Sympathetic Outflow in Pathological Conditions and Therapeutic Potential

Conclusion and Perspectives

Chapter 16: Metabolic Effects of AT 2 R Stimulation in Adipose Tissue

Metabolic Function of AT 2 R: The Lessons from ARBs

Metabolic Function of AT 2 R: The Lessons from AT 2 R-Deficient Mice

Metabolic Function of AT 2 R: Experiments with Direct AT 2 R Stimulation

References.

Chapter 17: Sex Differences in AT 2 R Expression and Action

Basis for Sex Differences in Function

AT 2 R Gene Mapping

Hormonal Regulation of AT 2 R Expression

Regulation of Arterial Pressure and Renal Function

Arterial Pressure

Kidney

Evidence for a Differential Role for the AT 2 R in Other Disease Conditions

Heart and Vascular Disease

Neurological Disorders

Reproduction

Chapter 18: Discovery of Nonpeptide, Selective AT 2 Receptor Agonists

Selective Drug-like AT 2 R Agonists from Nonpeptide, Nonselective AT 1 /AT 2 Receptor Ligands

Selective Drug-like AT 2 R Agonists from the Nonselective Parent Peptide Ang II

Conversion of AT 2 R Agonists to AT 2 R Antagonists

Chapter 19: Angiotensin-Based Peptides as AT 2 R Agonists

Endogenous Angiotensin Peptides

Ang II

Ang III

Ang IV

Ang 1-7

Ang 1-9

Synthetic Peptides

CGP42112

β -Amino-Acid-Substituted Angiotensin Peptides

[Y] 6 -AII

LP2-3 (dKcAng-(1-7))

Novokinin

Chapter 20: Potential Clinical Application of Angiotensin 2 Receptor Agonists

Preclinical Testing

Investigational New Drug Application

Clinical Trials

Potential Therapeutic Indications for AT 2 R Agonists

Orphan Indications

Marfan Syndrome

Idiopathic Pulmonary Fibrosis

Other Indications

Chapter 21: Angiotensin-(1-7) and Mas: A Brief History

Discovery of Mas: Is It a Proto-Oncogene?

Functions of Mas: Is It an Ang II Receptor?

Mas, Its Antisense RNA, and Imprinting

Mas Expression

Mas Functions: Mas-Deficient Mice

Discovery of Ang-(1-7)

Closing the Gap: Mas Is an Ang-(1-7) Receptor

Chapter 22: Animal Models with a Genetic Alteration of the ACE2/Ang-(1-7)/Mas Axis

Transgenic Animal Technology: A Brief Update

Transgenic and KO Rodent Models of the ACE2/Ang-(1-7)/Mas Axis

ACE2 Models

ACE2 KO Mice

Human ACE2 Overexpression in Mouse

Human ACE2 Overexpression in the Mouse Brain

Human ACE2 Overexpression in the Mouse Heart

Human ACE2 Overexpression in Mouse Podocytes

Human ACE2 Overexpression in the Rat Vascular Smooth Muscle

Mas Models

Mas-KO Mice

Mas Overexpression in Retina

Prolylcarboxypeptidase KO Mice

Ang-(1-7) Models

Transgenic Rats Overexpressing Ang-(1-7)

Transgenic Mice and Rats Overexpressing Ang-(1-7) in the Heart

Conclusions and Outlook

Chapter 23: Mas Signaling: Resolved and Unresolved Issues

Expression of Mas

Mas as a GPCR

Early Discovery of Mas and Its Signaling Pathways

Identifying Ang-(1-7) Targets Through Proteomics

Ang-(1-7)/Mas Signaling Through Akt

Ang-(1-7)/Mas Signaling and Nitric Oxide Production

Mas and MAPK Signaling

Mas and RhoA

Biological Significance of Mas Signaling: Insights from Mas-Knockout Mice

Unresolved Issues

Chapter 24: Mas/AT 2 Cross Talk

Chapter 25: ACE2 Cell Biology, Regulation, and Physiological Functions

ACE2: Discovery and Basic Biology

ACE2 Regulation

Chapter 26: Mas in Myocardial Infarction and Congestive Heart Failure

Myocardial Infarction and Congestive Heart Failure

Renin-Angiotensin System and Cardiac Remodeling

Inflammatory Phase

Proliferative Phase

Maturation Phase

Chapter 27: Mas Receptor: Vascular and Blood Pressure Effects

Chapter 28: Mas and Neuroprotection in Stroke

Introduction.

Neuroprotection and the RAS.

Notes:

Includes bibliographical references at the end of each chapters and index.

Description based on print version record.

Description based on publisher supplied metadata and other sources.

ISBN:

0-12-801364-8

OCLC:

908074996