Edward D. Frohlich – författare

This issue of Medical Clinics, guest edited by Dr. Edward Frohlich, is devoted to Hypertension. Articles in this outstanding issue include The Kidney in Hypertension; Heart: Fibrosis, Apoptosis, and Cardiac Failure; Myocardial Ischemia; Oxidative Stress and Hypertensive Diseases; Adherence to Antihypertensive Therapy; Aging and Hypertension; Target Organs and Microbiological Considerations in Hypertensive Diseases; Obesity and Sodium Considerations; Diabetes, Hypertension and Cardiorenal Syndrome; Renal Arterial Disease; Cardiac Transplantation and Hypertensive Diseases; Cardiac Failure: Old and New Challenges; Diastolic Dysfunction and Hypertension; Stiffening of Large Arteries; Genetics and Mechanisms; New Guidelines for Hypertensive Diseases; and Local Renin Angiotensin Systems.

How exciting it is to see a field so well established as the ren- angiotensin system continue to grow and mature. Originally, following the original identification of renin by Tigerstedt and Bergman over 100 years ago, workers in this area spent years attempting to establish its role in experimental and renal hypertension. The early work by Goldblatt, in 1934, demonstrated that the placement of a clip around a renal artery was clearly related to the subsequent development of hypertension. However, it wasn''t until the simultaneous finding by two different geographically separated teams, Page, et al, in the United States and Braun-Menendez, et al, in Argentina that the peptide angiotensin was identified. Thus, the rate-limiting enzyme renin was released from the kidney and catalyzed a biochemical cascade which was eventually shown to produce the elevated arterial pressure. Subsequently, many workers contributed to the elucidation of the concept and sequence of angiotensin I1 generation. Thus, the enzyme renin acted upon its protein substrate, produced in the liver, to liberate the decapeptide angiotensin I which, upon circulating through the pulmonary circulation, finally produced the potent octapeptide angiotensin. Several important subsequent findings demonstrated that angiotensin I1 promoted the release of the adrenal corticosteroid from that gland, thereby resulting in a larger system, the renin-angiotensin-aldosterone system. Further, this system demonstrated a classical biofeedback and the circulating octapeptide was shown to have additional biological activities in organs other than heart, vessels, kidney, adrenals, and even brain.

This issue of the Medical Clinics of North America brings the practicing clinician up to date on the current challenges, new concepts, and management of hypertensive disease. Topics covered include risks in hypertension; new biological concepts of target organ involvement in hypertension; hypertension and the metabolic syndrome; aging versus hypertension; hypertension, systolic blood pressure, and large arteries; oxidative stress, endothelial dysfunction, and hypertension; current thinking about hypertensive heart disease; diastolic dysfunction as a link between hypertension and heart failure; hypertension and cardiac failure in its various forms; hypertension and atherogenesis; the kidney, hypertension, and remaining challenges; current thinking about renovascular hypertension; obesity and hypertension; and barriers to adherence in hypertension management.

With great pleasure we present our Third International Workshop on The Local C- diac Renin–Angiotensin–Aldosterone System (RAAS), held at the Ochsner Clinic Foundation in November 2008. When this meeting was rst organized in 2002, we were pleased that all who were invited to participate in our rst workshop attended our program; and what is most satisfying, all of these participants returned for the second and this, the third workshop. In addition, we are delighted that a number of additional workers in this growing eld of investigation joined us for this third program. Over the years since our rst workshop, there is little doubt as to the existence of a local RAAS in the heart. Indeed, there is substantial evidence as to the existence of other local systems in brain, vessels, adrenal, and, as presented in the current workshop, the kidneys. What is even more stimulating intellectually, through dup- cation of local RAAS systems a remarkable yin-yang biological balance is provided by nature. Thus, in the current third workshop considerable evidence has accu- lated over the years for complicated local systems that serve to provide exquisite and unique local control of local organ functions.

With great pleasure we present our Third International Workshop on The Local C- diac Renin–Angiotensin–Aldosterone System (RAAS), held at the Ochsner Clinic Foundation in November 2008. When this meeting was rst organized in 2002, we were pleased that all who were invited to participate in our rst workshop attended our program; and what is most satisfying, all of these participants returned for the second and this, the third workshop. In addition, we are delighted that a number of additional workers in this growing eld of investigation joined us for this third program. Over the years since our rst workshop, there is little doubt as to the existence of a local RAAS in the heart. Indeed, there is substantial evidence as to the existence of other local systems in brain, vessels, adrenal, and, as presented in the current workshop, the kidneys. What is even more stimulating intellectually, through dup- cation of local RAAS systems a remarkable yin-yang biological balance is provided by nature. Thus, in the current third workshop considerable evidence has accu- lated over the years for complicated local systems that serve to provide exquisite and unique local control of local organ functions.

In cardiovascular prevention, there is classically a small number of cardiovascular risk factors to treat, such as hypertension, diabetes, hyperlipidemia and smoking excess, which are widely detected and treated. Recently, it has been widely recognized that new mechanical factors should be detected and treated and involves specifically pulsatile arterial hemodynamic (PAH) parameters such as: arterial stiffness, pulse pressure, and, to a lesser extent, augmentation index and pulse pressure amplification. The pedagogic aspect of this new CV specialty involves 3 principal parts: a. –Basic concepts and pathophysiological mechanisms of PAHb. –Clinical aspects and end-organ damage in PAHc. – Clinical pharmacology and therapeutics of PAH This book represents the first that spans basic science and clinical management of this new CV subspecialty. Much has been learned regarding the management of these patients in recent years and this book presents extensive data on the techniques needed to maximize outcomes.​

In cardiovascular prevention, there is classically a small number of cardiovascular risk factors to treat, such as hypertension, diabetes, hyperlipidemia and smoking excess, which are widely detected and treated. Recently, it has been widely recognized that new mechanical factors should be detected and treated and involves specifically pulsatile arterial hemodynamic (PAH) parameters such as: arterial stiffness, pulse pressure, and, to a lesser extent, augmentation index and pulse pressure amplification. The pedagogic aspect of this new CV specialty involves 3 principal parts: a. –Basic concepts and pathophysiological mechanisms of PAHb. –Clinical aspects and end-organ damage in PAHc. – Clinical pharmacology and therapeutics of PAH This book represents the first that spans basic science and clinical management of this new CV subspecialty. Much has been learned regarding the management of these patients in recent years and this book presents extensive data on the techniques needed to maximize outcomes.​

In cardiovascular prevention, there is classically a small number of cardiovascular risk factors to treat, such as hypertension, diabetes, hyperlipidemia and smoking excess, which are widely detected and treated. Recently, it has been widely recognized that new mechanical factors should be detected and treated and involves specifically pulsatile arterial hemodynamic (PAH) parameters such as: arterial stiffness, pulse pressure, and, to a lesser extent, augmentation index and pulse pressure amplification. The pedagogic aspect of this new CV specialty involves 3 principal parts: a. –Basic concepts and pathophysiological mechanisms of PAHb. –Clinical aspects and end-organ damage in PAHc. – Clinical pharmacology and therapeutics of PAH This book represents the first that spans basic science and clinical management of this new CV subspecialty. Much has been learned regarding the management of these patients in recent years and this book presents extensive data on the techniques needed to maximize outcomes.​

With great pleasure we present our Third International Workshop on The Local C- diac Renin–Angiotensin–Aldosterone System (RAAS), held at the Ochsner Clinic Foundation in November 2008. When this meeting was rst organized in 2002, we were pleased that all who were invited to participate in our rst workshop attended our program; and what is most satisfying, all of these participants returned for the second and this, the third workshop. In addition, we are delighted that a number of additional workers in this growing eld of investigation joined us for this third program. Over the years since our rst workshop, there is little doubt as to the existence of a local RAAS in the heart. Indeed, there is substantial evidence as to the existence of other local systems in brain, vessels, adrenal, and, as presented in the current workshop, the kidneys. What is even more stimulating intellectually, through dup- cation of local RAAS systems a remarkable yin-yang biological balance is provided by nature. Thus, in the current third workshop considerable evidence has accu- lated over the years for complicated local systems that serve to provide exquisite and unique local control of local organ functions.

Experimental and clinical evidence supports the view that the activation of the renin angiotensin aldosterone system is involved in cardiovascular pathology including hypertension, heart failure, myocardial ischemia, and atherosclerosis. The present volume describes the intricacies involved in these processes, including the in?uence of prorenin/renin, angiotensin II, angiotensin (1-7), and aldosterone on cardiac and vascular functions as well as their involvement in the generation of cardiovascular diseases. Fundamental aspects like intracellular signaling, regulation of cell volume in the failing heart, and the presence of an intracrine renin angiotensin system are discussed. Moreover, the role of the mineralocorticoid receptor as an important c- ponent of the intracrine renin angiotensin system and as a regulator of extracellular action of angiotensin II is described, reinforcing the view that aldosterone inhibitors are helpful in the treatment of heart failure and hypertension. Let us hope the imp- tant topics included here motivate basic and clinical investigators and contribute to the development of new therapeutic approaches for cardiovascular diseases.We want to thank the distinguished authors and Humana Press for the opportunity to publish this important book. Walmor C. DeMello Edward Frohlich v Contents 1 Systemic Versus Local Renin Angiotensin Systems. An Overview ...1 Walmor C. DeMello and Richard N. Re 2 Clinical Import of the Local Renin Angiotensin Aldosterone Systems ...7 Edward D. Frohlich 3 Renin, Prorenin, and the (Pro)Renin Receptor ...15 Genevieve Nguyen and Aurelie Contrepas 4 Local Renin Angiotensin Systems in the Cardiovascular System ...25 Richard N.