Endothelin in Renal Physiology and Disease

Endothelin in Renal Physiology and Disease PDF

Author: M. Barton

Publisher: Karger Medical and Scientific Publishers

Published: 2011-09-01

Total Pages: 276

ISBN-13: 3805597959

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Endothelin is a 21-amino acid peptide that exerts uniquely potent and long-lasting effects on the kidney, including regulation of water and electrolyte excretion, blood pressure, cell growth, inflammation and fibrosis. During the past 10 years, the field has evolved rapidly; we are now uncovering the potential importance of endothelin receptor antagonists (ERAs) in the treatment of kidney disease.This book reviews experimental concepts, preclinical studies and clinical data which form the basis of our current understanding of the association between endothelin and kidney disease. Acclaimed experts in pharmacology, molecular biology, physiology, cardiovascular medicine, and nephrology have contributed timely reviews dealing with renal pharmacology and physiology of endothelin, the role of endothelin in renal disease development and ERAs in preclinical studies, and the current state of clinical development of ERA therapy in renal medicine.The publication at hand will be a valuable reference source for nephrologists, internists and other healthcare professionals, renal physiologists and molecular biologists, post-doctoral researchers and students in the life sciences, as well as for scientists and decision makers in drug research and development.

Endothelin in the Kidney

Endothelin in the Kidney PDF

Author: David Pollock

Publisher: Biota Publishing

Published: 2011-11-01

Total Pages: 90

ISBN-13: 1615042113

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The discovery of a potent vasoconstrictor, endothelin (ET)-1, derived from vascular endothelial cells was among a variety of key lines of investigation that helped to fuel a major explosion of studies related to endothelial cell biology. This was particularly evident within the pharmaceutical industry where receptor antagonists were quickly developed and are now on the market for treatment of pulmonary hypertension and in development for other diseases such as diabetic nephropathy and cancer. Importantly, we know that the kidney contains the highest level of ET-1 production and receptor expression in the body where it has been demonstrated to function as a pro-natriuretic autocrine and paracrine factor that is activated in conditions of high salt intake. This eBook provides a review of the various mechanisms whereby ET-1 has been shown to function within the kidney through a wide range of actions that include direct effects on tubular transport, intrarenal hemodynamics, as well as neural and endocrine functions. Much has yet to be discerned, but it is clear that the ET system is a major physiological regulator of fluid-electrolyte balance and blood pressure through these renal actions. Table of Contents: Discovery of Endothelin / Basic Biology of the Endothelin System / Renal Localization / Renal Hemodynamics / Renal Tubular Actions of Endothelin / Endothelin in Neural Modulation of Renal Function / Physiological Role of Endothelin / Endothelin in Renal Pathology / References / Author Biographies

The Endothelium

The Endothelium PDF

Author: Michel Félétou

Publisher: Morgan & Claypool Publishers

Published: 2011

Total Pages: 309

ISBN-13: 1615041230

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The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

Neural Control of Renal Function, Second Edition

Neural Control of Renal Function, Second Edition PDF

Author: Ulla C. Kopp

Publisher: Biota Publishing

Published: 2018-07-17

Total Pages: 122

ISBN-13: 161504776X

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The kidney is innervated with efferent sympathetic nerve fibers reaching the renal vasculature, the tubules, the juxtaglomerular granular cells, and the renal pelvic wall. The renal sensory nerves are mainly found in the renal pelvic wall. Increases in efferent renal sympathetic nerve activity reduce renal blood flow and urinary sodium excretion by activation of α1-adrenoceptors and increase renin secretion rate by activation of β1-adrenoceptors. In response to normal physiological stimulation, changes in efferent renal sympathetic nerve activity contribute importantly to homeostatic regulation of sodium and water balance. The renal mechanosensory nerves are activated by stretch of the renal pelvic tissue produced by increases in renal pelvic tissue of a magnitude that may occur during increased urine flow rate. Under normal conditions, the renal mechanosensory nerves activated by stretch of the sensory nerves elicits an inhibitory renorenal reflex response consisting of decreases in efferent renal sympathetic nerve activity leading to natriuresis. Increasing efferent sympathetic nerve activity increases afferent renal nerve activity which, in turn, decreases efferent renal sympathetic nerve activity by activation of the renorenal reflexes. Thus, activation of the afferent renal nerves buffers changes in efferent renal sympathetic nerve activity in the overall goal of maintaining sodium balance. In pathological conditions of sodium retention, impairment of the inhibitory renorenal reflexes contributes to an inappropriately increased efferent renal sympathetic nerve activity in the presence of sodium retention. In states of renal disease or injury, there is a shift from inhibitory to excitatory reflexes originating in the kidney. Studies in essential hypertensive patients have shown that renal denervation results in long-term reduction in arterial pressure, suggesting an important role for the efferent and afferent renal nerves in hypertension.

Endothelin System & Its Antagonism in Chronic Kidney Disease

Endothelin System & Its Antagonism in Chronic Kidney Disease PDF

Author: Neeraj Dhaun

Publisher:

Published: 2012

Total Pages: 156

ISBN-13:

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Since its discovery in 1988 the powerful vasoconstrictor endothelin-1 (ET-1) has been widely implicated in the pathophysiology of chronic kidney disease (CKD) as well as the cardiovascular disease with which it is associated. ET receptor antagonists have favourable effects in experimental models of these conditions and orally acting antagonists are now licensed for the treatment of pulmonary arterial hypertension. However, there is a paucity of human data regarding the role of ET-1 in CKD. In this thesis, I have therefore explored the utility of ET-1 as a biomarker in CKD, and, using selective ET receptor antagonists, the beneficial renal and cardiovascular effects of ET receptor antagonism in CKD. I have shown that as glomerular filtration rate (GFR) declines plasma ET-1 increases linearly whereas urinary ET-1 shows an exponential increase. Furthermore, urinary ET-1 may be a useful marker of disease activity in patients with lupus nephritis. Its levels are high in those with biopsy-proven active renal inflammation and these fall with treatment. I have shown that in subjects with stable non-diabetic proteinuric CKD, acute selective ETA receptor antagonism reduces blood pressure and arterial stiffness and that these systemic benefits are associated with an increase in renal blood flow and reduction in proteinuria. Importantly, these effects are seen on top of those achieved with maximal therapy with angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers. Following a study confirming unchanged pharmacokinetics in CKD, I have used an oral selective ETA receptor antagonist to show that the reductions in BP, arterial stiffness and proteinuria seen in my acute studies are maintained longer term. This results of this study also suggest that the mechanism for the reduction in proteinuria is haemodynamic and relates to a reduction in GFR and filtration fraction. In summary, these studies suggest that ET-1 may act as a potential biomarker of renal inflammation, and confirm its role in the pathophysiology of the systemic and renal vasoconstriction seen in CKD. They also suggest that selective ETA receptor antagonism may provide a novel therapeutic approach in proteinuric CKD on top of standard therapies. Larger and longer term studies are now warranted to confirm this potential.

Pediatric Kidney Disease

Pediatric Kidney Disease PDF

Author: Denis F. Geary

Publisher: Springer

Published: 2017-02-16

Total Pages: 1968

ISBN-13: 3662529726

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The new edition of this valuable clinical resource offers a state of the art, comprehensive review on every clinical condition encountered in pediatric nephrology. International experts present the latest knowledge on epidemiology, diagnosis, management, and prognosis in one concise, clinically focused text, in which care has been taken to couple just the right amount of "need-to-know" basic science with practical clinical guidance that will enable the reader to make efficient, informed decisions. The topics covered include: disorders of renal development, glomerular disorders, the kidney and systemic disease, renal tubular disorders, tubulointerstitial disease, urinary tract disorders, acute kidney injury, hypertension, chronic and end-stage renal disease, and renal replacement therapy. The full-color, highly visual, meticulously crafted format will ensure that the practitioner is able to source and apply information with remarkable ease.

The Endothelins

The Endothelins PDF

Author: Winifred G. Nayler

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 193

ISBN-13: 364275872X

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"What we call the beginning is often the end, and to make an end is to make a beginning. The end is where we start from." T. S. ELIOT, "Geroniton" The discovery of endothelin-l was both an end and a beginning. It is an end because this discovery has started a plethora of investigations as to endothe1in's sites of production, mode of action, it's normal and abnormal physiological role and its involvement in a variety of pathological conditions ranging from renal failure to myocardial infarction, cardiac hypertrophy, hyperten sion, cyclosporine induced toxicity, mental depression, renal failure, stress related illness, and even stroke and sudden death. It is a beginning because no one can foresee where the investigations will ultimately lead, or how they will end. The discovery of the endothelins was a very recent event and soon specialist books will start to appear dealing in detail with different aspects of their chemistry, physiological role and pathological importance. The present book is intended to act as a guide and primer for those who are becoming intrigued by the many endothelin related articles which are now appearing in the journals but who as yet have not had the time or opportunity to be caught up in the web of enthusiasm and excitement which is motivating those more directly involved in the field of research.

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