 |
|
Key player identified in cascade that leads to hypertension-related kidney damage
November 06, 2009AUGUSTA, Ga. - A key player in a cascade that likely begins with stress and leads to high blood pressure and kidney damage has been identified by researchers who say the finding may lead to better ways to control both.
Medical College of Georgia researchers have found endothelin, a powerful blood vessel constrictor and inflammatory peptide, increases the number of T cells in the kidneys, which helps recruit other immune cells, causing inflammation and destruction.
"We think that endothelin somehow causes an increase in T cells which results in renal injury which makes the hypertension worse and harder to control," says Dr. Karthik Krishnan, an MCG allergy/immunology fellow who presents the findings during the 2009 American College of Allergy, Asthma & Immunology Annual Meeting Nov. 5-9 in Miami. Dr. Krishnan was honored with one of three Clement von Pirquet Awards for best scientific paper in allergy/immunology presented by fellows-in-training at the meeting.
The process likely begins in some people when stress, diet or other factors raise levels of the hormone angiotensin II, another powerful blood vessel constrictor, which, in turn, increases endothelin levels. Researchers don't know why endothelin increases T-cell levels in the kidneys. "There are still a lot of mechanistic questions we have," notes Dr. Krishnan.
Inflammation, a part of the normal healing process, also is increasingly identified as a major contributor to a variety of diseases from cancer to cardiovascular disease. "We are starting to look at inflammatory mediators or processes that make hypertension worse with the long-term goal of finding interventions or therapies to counteract these mediators and better control hypertension and prevent organ damage," Dr. Krishnan says.
It's a subset of patients - with mostly uncontrolled hypertension, likely because of a combination of environment and genetics - that tend to have more inflammation and more resulting kidney damage. Dr. Krishnan hopes that making the endothelin connection will one day help identify these people before their kidneys take a beating.
Standard urinalysis can detect protein in the urine, one of the first signs sign that "the kidneys are falling down on the job," says Dr. David Pollock, renal physiologist in MCG's Vascular Biology Center and a study co-author. "It's like a cheesecloth that is old and worn out and the holes are getting too big." The body should use all the protein it makes or consumes so none should show up in urine
For the study, mice with normal blood pressures got angiotensin II, which raised their blood pressure and the T cell count in their kidneys. But when researchers also gave an endothelin blocker, T cells numbers in the kidneys did not increase. To double-check the findings, they gave angiotensin II to mice that can't make endothelin and the T cell count stayed down, the researchers report.
For at-risk individuals, endothelin blockers, already on the market for pulmonary hypertension and under study for some other conditions that result in kidney failure, may help avoid the destruction, Dr. Pollock says.
"We're optimistic that it's important in other forms of renal disease. It looks like this could be useful for essentially anyone with protein in the urine. That's what's really exciting about it," he says.
Medical College of Georgia
The process likely begins in some people when stress, diet or other factors raise levels of the hormone angiotensin II, another powerful blood vessel constrictor, which, in turn, increases endothelin levels. Researchers don't know why endothelin increases T-cell levels in the kidneys. "There are still a lot of mechanistic questions we have," notes Dr. Krishnan.
Inflammation, a part of the normal healing process, also is increasingly identified as a major contributor to a variety of diseases from cancer to cardiovascular disease. "We are starting to look at inflammatory mediators or processes that make hypertension worse with the long-term goal of finding interventions or therapies to counteract these mediators and better control hypertension and prevent organ damage," Dr. Krishnan says.
It's a subset of patients - with mostly uncontrolled hypertension, likely because of a combination of environment and genetics - that tend to have more inflammation and more resulting kidney damage. Dr. Krishnan hopes that making the endothelin connection will one day help identify these people before their kidneys take a beating.
Standard urinalysis can detect protein in the urine, one of the first signs sign that "the kidneys are falling down on the job," says Dr. David Pollock, renal physiologist in MCG's Vascular Biology Center and a study co-author. "It's like a cheesecloth that is old and worn out and the holes are getting too big." The body should use all the protein it makes or consumes so none should show up in urine
For the study, mice with normal blood pressures got angiotensin II, which raised their blood pressure and the T cell count in their kidneys. But when researchers also gave an endothelin blocker, T cells numbers in the kidneys did not increase. To double-check the findings, they gave angiotensin II to mice that can't make endothelin and the T cell count stayed down, the researchers report.
For at-risk individuals, endothelin blockers, already on the market for pulmonary hypertension and under study for some other conditions that result in kidney failure, may help avoid the destruction, Dr. Pollock says.
"We're optimistic that it's important in other forms of renal disease. It looks like this could be useful for essentially anyone with protein in the urine. That's what's really exciting about it," he says.
Medical College of Georgia
Endothelin Current Events and Endothelin News RSSEndothelin-1 inhibitors in chronic pancreatitis
Fibrosis is a key feature of chronic pancreatitis and pancreatic cancer. The extensive deposition of extracellular matrix proteins fosters the development of an exocrine and endocrine organ insufficiency, and accelerates progression of the tumour.
Males May Experience Greater Physical Pain Due To Lower Levels Of A Key Protein, Endothelin
Agonizing physical pain, known as vaso-occlusive pain, can afflict children who have sickle cell disease (SCD).
Endothelin-Related Drugs Benefit Patients With Pulmonary Hypertension
Recent research to block the effects of endothelin, a powerful substance that constricts blood vessels and stimulates cell growth, has led to successful treatment of pulmonary arterial hypertension and provides hope for treating other chronic diseases.
International conference on endothelin
One of the most intriguing developments in recent medical science is the discovery of the human chemical endothelin (ET).
Arterial, venous or total mesenteric ischemia/reperfusion causes different types of injury?
It is known that I/R induces an inflammatory response deleterious to the organ involved but also to the system as a whole.
Blood flow in Alzheimer's disease
Researchers have discovered that the enzyme, endothelin converting enzyme-2 (ECE-2), may cause the decrease in blood flow in the brain seen in Alzheimer's disease and contribute to progression of the disease.
Will IVF work for a particular patient? The answer may be found in her blood
For the first time, researchers have been able to identify genetic predictors of the potential success or failure of IVF treatment in blood.
Researchers may have found why women have an edge on salt-sensitive hypertension
Researchers may have found why women have an edge in keeping a healthier balance between the amount of salt they eat and excrete - at least before reaching menopause.
Mechanisms of cardiovascular disease and cancer give clues to new therapies
Cardiovascular conditions leading to heart attacks and strokes are treated quite separately from common cancers of the prostate, breast or lung, but now turn out to involve some of the same critical mechanisms at the molecular level.
Study shows pine bark naturally reduces cardiovascular risk factors in diabetics
A new study published in the May 2008 (volume 8, issue 25) edition of the journal of Nutrition Research shows Pycnogenol (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree, reduces blood sugar in type II diabetes patients, allows people to lower their antihypertensive medication and improves cardiovascular disease (CVD) risk factors.
More Endothelin Current Events and Endothelin News Articles
 |
Endothelin Protocols (Methods in Molecular Biology, 206) (Methods in Molecular Biology) by Janet J. Maguire (Editor), Anthony P. Davenport (Editor) A panel of multidisciplinary experts describes in detail readily reproducible methods to investigate all aspects of the endothelin system from its synthesis and metabolism, to its function in health and disease. Theses methods use state-of-the-art molecular techniques to quantify the expression of mRNA for both endothelin receptors and the endothelin converting enzymes. They show how peptides, precursors, receptors, and synthetic enzymes can be localized and quantified in plasma, culture supernatants, tissue homogenate, and tissue sections using antibodies. Several in vivo protocols illustrate the role of the endothelin peptides in healthy human individuals and describe animal models that can be used to predict the therapeutic potential of cardiovascular drugs that manipulate... |
 |
Endothelin Receptors: From the Gene to the Human (Pharmacology and Toxicology) by Robert R. Ruffolo (Editor) Since the discovery of endothelin, major advances have been made in understanding the molecular structure and function of the endothelin receptors. At least two subtypes of receptors, designated ETA and ETB, have been identified through biochemical and pharmacological techniques. These subtypes are cloned and expressed and additional subtypes appear to exist. The biochemical events involved in the signal transduction processes that ultimately activate the cellular machinery involved in the end-organ responses are presented, as are the mechanisms by which the receptors recognize specific and different G-proteins. Functions mediated by the receptors at the cellular, tissue and, organ level are reviewed in detail, as well as the roles that they may play a part in the physiologic and... |
 |
Endothelin: Tole in Health & by GULATI (Author) Endothelin summarizes the progress made in the field of endothelin research since its discovery. Initially it was believed to have vasoactive properties, however it is now known that endothelin, as well as vasculature, is involved in many other systems. Care has been taken to include almost all major systems into the text. The book focuses on the role of endothelin in the pathophysiology of several diseases, both cardiovascular and non-cardiovascular, and its role in inflammation. Endothelin interaction with a variety of other regulatory agents is discussed, providing a text which will be of great value to scientists engaged in studies on this multifunctional polypeptide. |
 |
Endothelins in Biology and Medicine by John P. Huggins (Author), John T. Pelton (Author) Endothelin-1 (ET-1), a peptide discovered in 1988, is one of the most potent contractors of vascular smooth muscle. Since their discovery, ETs have generated enormous interest in the scientific and pharmaceutical communities, prompting extensive research. This book addresses the latest findings regarding ETs-how they function, their effects, and characteristics. Divided into five sections, the book covers: endothelin receptors, endothelin synthesis and degradation, endothelin pathophysiology, ligand structure and activity relationships, and clinical studies. Pharmacologists, toxicologists, and pharmaceutical researchers will all benefit from this thorough review of current findings and future directions in ET research. |
 |
Endothelin Receptors and Signaling Mechanisms (Biotechnology Intelligence Unit) by David M. Pollock (Editor), Robert F. Highsmith (Editor) This book focuses on the wide variety of intracellular events that occur as a result of endothelin receptor activation. This includes a discussion of the various pathways by which endothelin activates Ca2+ signals from several intra- and extracellular sources and the effects of endothelin on ion channels and membrane function. In addition, the mechanisms by which endothelin influences the ion transport within the renal epithelium are covered, as well as the signal transduction pathways activated by endothelin in both cardiac tissue and vascular smooth muscle. |
|
Endothelin (Clinical Physiology Series) by Gabor M. Rubanyi (Editor) Merely three years after the discovery of endothelin, a large amount of information has been generated about the molecular biology, biosynthesis, biological actions and potential physiological and pathological importance of this unique peptide and its isoforms. This first book on endothelins summarizes the early events which lead to the discovery of endothelin, the progress made in understanding the peptide's physiological role, and the current state-of-the-art in contemporary endothelin research. The book also discusses the potential significance of endothelins in health and disease, covers the potential role of the peptides in the integrated control of the cardiovascular system, and outlines future research directions. This comprehensive monograph is an indispensable reference for basic... | |
 |
Endothelin: Webster's Timeline History, 1988 - 2007 by Icon Group International (Author) Webster's bibliographic and event-based timelines are comprehensive in scope, covering virtually all topics, geographic locations and people. They do so from a linguistic point of view, and in the case of this book, the focus is on "Endothelin," including when used in literature (e.g. all authors that might have Endothelin in their name). As such, this book represents the largest compilation of timeline events associated with Endothelin when it is used in proper noun form. Webster's timelines cover bibliographic citations, patented inventions, as well as non-conventional and alternative meanings which capture ambiguities in usage. These furthermore cover all parts of speech (possessive, institutional usage, geographic usage) and contexts, including pop culture, the arts, social sciences... |
 |
Endothelins: Webster's Facts and Phrases by Icon Group International (Author) Ever need a fact or quotation on "endothelins"? Designed for speechwriters, journalists, writers, researchers, students, professors, teachers, historians, academics, scrapbookers, trivia buffs and word lovers, this is the largest book ever created for this word. It represents a compilation of "single sentences" and/or "short paragraphs" from a variety of sources with a linguistic emphasis on anything relating to the term "endothelins," including non-conventional usage and alternative meanings which capture ambiguities. This is not an encyclopedic book, but rather a collage of statements made using the word "endothelins," or related words (e.g. inflections, synonyms or antonyms). This title is one of a series of books that considers all major vocabulary words. The entries in each book... |
 |
Einfluß von Endothelin-1 auf Kontraktionskraftentwicklung und intrazelluläre Calcium-Homöostase des Myokards by Matthias Zirnig (Author) |
 |
Pulmonary Actions of the Endothelins (Respiratory Pharmacology and Pharmacotherapy) by Goldie (Editor), Hay (Editor) This book addresses the subject of the biology of the endothelin peptides in the lung, with particular reference to the respiratory tract and the possible mediator roles of these peptides in lung disease. The book provides an up-to-date analysis of the current literature concerning the actions of the endothelins in the lung. Specific chapters are devoted to our current understanding of endothelin synthesis, receptor subtype activation, distribution and density in the airways, its actions in vascular and airway smooth muscle and nerves and its role in tissue development, differentiation and disease. This volume will be of interest to both nonclinical and clinical researchers in pulmonary biology, as well as to teachers in academic disciplines targetting aspects of lung function and... |
| © 2009 BrightSurf.com |