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 and procoagulant states.

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 diabetes with some agents.

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 chapter to this topical and highly critical subject.

#### **Samy I. McFarlane, MD, MPH, MBA, FACP** Distinguished Teaching Professor and Associate Dean, Internal Medicine Residency Program Director, College of Medicine,

Department of Medicine, Division of Endocrinology, State University of New York, Downstate Health Science University, New York, USA

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