Meet the editor

Dr. McFarlane is a Distinguished Teaching Professor of Medicine/Endocrinology and Associate Dean at SUNY-Downstate, Health Sciences University, Brooklyn, New York, USA. He has extensive experience in clinical and translational research and served as the PI for the largest center in North America in the landmark Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial. He is the author of more

than 400 publications with more than 10,000 citations and an h-index of 46. He also has 270 highly influential citations to his credit, including those in major guidelines by the American Heart Association (AHA), such as stroke guidelines (2018 and 2019), the Scientific Statement from the AHA on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation 2020, and the 2021 SHNE/HRS/EHRA/ APHRS Expert Collaborative Statement. He is also the editor of several books on diabetes, hypertension, cardiovascular disease, and related topics. Dr. McFarlane is a three-term member of the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NIDDK) and served twice as chair of the NIH-NIDDK U01 committee. He also served as chair of the clinical sub-committee of the National Kidney Foundation (NKF) Kidney Early Evaluation Program. Locally, he held several leadership positions including Medical Director of Clinical Research and Program Director and Chief of Endocrinology. He also served as District President of the American College of Physicians. Dr. McFarlane is the recipient of numerous awards and honors including recognition from the United States Army, the US Congress, and the Gold Foundation for Humanism in Medicine.

Contents

**Section 1**

*and Amgad N. Makaryus*

Processes: An Overview

*by A.H.M. Nurun Nabi and Akio Ebihara*

and Genetics

Hypertension *by Jose A. Gomez*

Alzheimer's Disease *by Vinothkumar Ganesan*

from Major Clinical Trials

*Deborah Osafehinti and Jocelyne Karam*

**Section 2**

**Preface III**

The Renin-Angiotensin Aldosterone System: Pathophysiologic Insights **1**

**Chapter 1 3**

**Chapter 2 21**

The Renin-Angiotensin Aldosterone System in Various Disorders **53**

**Chapter 3 55**

**Chapter 4 79**

**Chapter 5 93**

**Chapter 6 103**

The Role of the Renin-Angiotensin-Aldosterone System in Cardiovascular

*by Violeta Capric, Harshith Priyan Chandrakumar, Jessica Celenza-Salvatore* 

Diabetes and Renin-Angiotensin-Aldosterone System: Pathophysiology

Role of the Renin-Angiotensin-Aldosterone System in Various Disease

Renin Angiotensin Aldosterone System Functions in Renovascular

The Role of Renin Angiotensin Aldosterone System in the Progression of Cognitive Dysfunction in Chronic Kidney Disease Patients with

Renin Angiotensin Aldosterone System, Glucose Homeostasis, and Prevention of Type 2 Diabetes: Mechanistic Insights and Evidence

*by Samara Skwiersky, Sandra Iwuala, Seeta Chillumuntala,* 

*by Volkan Gelen, Abdulsamed Kükürt and Emin Şengül*

Disease: Pathogenetic Insights and Clinical Implications

## Contents



Preface

While the Renin-Angiotensin Aldosterone System (RAAS) plays a central role in salt and water homeostasis, it also affects various organ systems including the heart and vasculature, the kidneys, and the nervous system. Evidence indicates that angiotensin II has major deleterious effects on vascular tone, insulin sensitivity, and markers of inflammation and thrombosis. RAAS overactivity is implicated in the pathogenesis of serious and commonly encountered disease entities including hypertension, type 2 diabetes, diabetic nephropathy, left ventricular hypertrophy, congestive heart failure (CHF), and myocardial infarction.

The major pathogenetic mechanisms resulting from RAAS overactivity include activation of the sympathetic nervous system, endothelial dysfunction, and proinflammatory

Evidence from basic science and major clinical trials established the beneficial effects of inhibitors of the different components of RAAS such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and aldosterone antagonists. RASS inhibition is currently utilized in the treatment of hypertension, diabetic nephropathy, and CHF. Inhibitors also demonstrated improvements in outcomes after myocardial infarction and improvement in glucose homeostasis as well as prevention of type 2

In this book, written by a group of highly experienced scholars, we address the major concepts and topics related to RAAS activation, including the pathogenetic mechanisms underlying the deleterious effects of activated RAAS and the role of local tissue RAAS in various organ systems such as the heart and vasculature, the skeletal muscle, adipose tissues, pancreas, and the angiotensinergic pathways in the brain. Cutting-edge information addresses the needs of a wide range of readers including medical students, clinical practitioners, and basic science investigators alike. This book bridges the gap between basic science and clinical practice regarding the RAAS system, which is imminently critical and highly relevant to today's practice of medicine. Finally, with data emerging from the COVID-19 pandemic indicating overrepresentation of people with diseases associated with RAAS activation such as hypertension, chronic kidney disease, and diabetes, the role of RAAS activation and RAAS inhibition in the pathogenesis and clinical outcomes in COVID-19 has garnered a great deal of interest. In this book, we dedicate a

**Samy I. McFarlane, MD, MPH, MBA, FACP**

Downstate Health Science University,

College of Medicine, Department of Medicine, Division of Endocrinology, State University of New York,

New York, USA

Distinguished Teaching Professor and Associate Dean, Internal Medicine Residency Program Director,

and procoagulant states.

diabetes with some agents.

chapter to this topical and highly critical subject.
