The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Frederic Jaisser - One of the best experts on this subject based on the ideXlab platform.
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Blood pressure and amiloride-sensitive Sodium channels in vascular and Renal cells
Nature Reviews Nephrology, 2014Co-Authors: David G. Warnock, Kristina Kusche-vihrog, Antoine Tarjus, Shaohu Sheng, Hans Oberleithner, Thomas R. Kleyman, Frederic JaisserAbstract:Renal perfusion pressure, glomerular filtration and net Renal Sodium Reabsorption maintain volume homeostasis Cell stiffness and myogenic tone contribute to peripheral vascular resistance in the presence of aldosterone and normal Sodium concentrations in the arterial circulation Structural similarities exist between the amiloride-sensitive Sodium channels in the epithelial and endothelial cells Distinctions based on functional differences, especially in response to changes in extracellular Sodium concentrations, might permit development of novel pharmacological approaches to differentially target epithelial and endothelial Sodium channels Agents that preferentially inhibit the vascular channels could lower systemic blood pressure without the associated inhibition of potassium secretion that accompanies the available Sodium channel blockers and mineralocorticoid receptor antagonists Blood pressure control is influenced by amiloride-sensitive Sodium channels in the vascular and epithelial homeostatic systems in the kidney. Here, the authors describe the expression and regulation of Sodium channels, and they outline the emerging evidence that differences between Sodium channel complexes expressed in the epithelia and endothelia might permit novel therapeutic approaches to lower systemic blood pressure without the adverse effects associated with the Sodium channel blockers that are currently available. Sodium transport in the distal nephron is mediated by epithelial Sodium channel activity. Proteolytic processing of external domains and inhibition with increased Sodium concentrations are important regulatory features of epithelial Sodium channel complexes expressed in the distal nephron. By contrast, Sodium channels expressed in the vascular system are activated by increased external Sodium concentrations, which results in changes in the mechanical properties and function of endothelial cells. Mechanosensitivity and shear stress affect both epithelial and vascular Sodium channel activity. Guyton's hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. The synergistic effects, and complementary regulation, of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and probably reflect sequential evolution of the two systems. The integration of vascular tone, Renal perfusion and regulation of Renal Sodium Reabsorption is the central underpinning of the Guytonian model. In this Review, we focus on the expression and regulation of Sodium channels, and we outline the emerging evidence that describes the central role of amiloride-sensitive Sodium channels in the efferent (vascular) and afferent (epithelial) arms of this homeostatic system.
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Blood pressure and amiloride-sensitive Sodium channels in vascular and Renal cells.
Nature reviews. Nephrology, 2014Co-Authors: David G. Warnock, Kristina Kusche-vihrog, Antoine Tarjus, Shaohu Sheng, Hans Oberleithner, Thomas R. Kleyman, Frederic JaisserAbstract:Sodium transport in the distal nephron is mediated by epithelial Sodium channel activity. Proteolytic processing of external domains and inhibition with increased Sodium concentrations are important regulatory features of epithelial Sodium channel complexes expressed in the distal nephron. By contrast, Sodium channels expressed in the vascular system are activated by increased external Sodium concentrations, which results in changes in the mechanical properties and function of endothelial cells. Mechanosensitivity and shear stress affect both epithelial and vascular Sodium channel activity. Guyton's hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. The synergistic effects, and complementary regulation, of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and probably reflect sequential evolution of the two systems. The integration of vascular tone, Renal perfusion and regulation of Renal Sodium Reabsorption is the central underpinning of the Guytonian model. In this Review, we focus on the expression and regulation of Sodium channels, and we outline the emerging evidence that describes the central role of amiloride-sensitive Sodium channels in the efferent (vascular) and afferent (epithelial) arms of this homeostatic system.
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The mineralocorticoid receptor as a novel player in skin biology: beyond the Renal horizon?
Experimental dermatology, 2009Co-Authors: Nicolette Farman, Frederic Jaisser, Eve Maubec, Burkhard Poeggeler, Jennifer E Klatte, Ralf PausAbstract:The mineralocorticoid receptor (MR) and its ligand aldosterone regulate Renal Sodium Reabsorption and blood pressure and much knowledge has been accumulated in MR physiopathology, cellular and molecular targets. In contrast, our understanding of this hormonal system in non-classical targets (heart, blood vessels, neurons, keratinocytes...) is limited, particularly in the mammalian skin. We review here the few available data that point on MR in the skin and that document cutaneous MR expression and function, based on mouse models and very limited observations in humans. Mice that overexpress the MR in the basal epidermal keratinocytes display developmental and post-natal abnormalities of the epidermis and hair follicle, raising exciting new questions regarding skin biology. The MR as a transcription factor may be an unexpected novel player in regulating keratinocyte and hair physiology and pathology. Because its activating ligand also includes glucocorticoids, that are widely used in dermatology, we propose that the MR may be also involved in the side-effects of corticoids, opening novel options for therapeutical intervention.
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Conditional transgenic mice for studying the role of the glucocorticoid receptor in the Renal collecting duct.
Endocrinology, 2008Co-Authors: Aurelie Nguyen Dinh Cat, Nicolette Farman, Antoine Ouvrard-pascaud, François Tronche, Maud Clemessy, Daniel Gonzalez-nunez, Frederic JaisserAbstract:The mineralocorticoid receptor (MR) is a major regulator of Renal Sodium Reabsorption and body fluid homeostasis. However, little is known about glucocorticoid receptor (GR)-dependent Renal effects. Glucocorticoids may activate both receptors, so it is difficult to distinguish between MR- and GR-mediated effects in vivo. To overcome this complexity, we used a transgenic mouse model allowing conditional GR overexpression (doxycycline inducible TetON system, Hoxb7 promoter) in the Renal collecting duct (CD) to identify GR-regulated genes involved in Sodium transport in the CD. In microdissected cortical CD, induction of GR expression led (after 2 d of doxycycline) to increased α-epithelial Sodium channel and glucocorticoid-induced leucine zipper and decreased abundance of with-no-lysine kinase 4 transcripts, without modification of Na,K-ATPase, serum- and glucocorticoid-kinase-1, or MR expression. No changes occurred in the upstream distal and connecting tubules [distal convoluted tubule (DCT), connecting t...
Thomas R. Kleyman - One of the best experts on this subject based on the ideXlab platform.
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Epithelial Sodium Channel and Salt-Sensitive Hypertension.
Hypertension (Dallas Tex. : 1979), 2021Co-Authors: Stephanie M Mutchler, Annet Kirabo, Thomas R. KleymanAbstract:The development of high blood pressure is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. Humans display a spectrum of Sodium-sensitivity, with some individuals displaying a significant blood pressure rise in response to increased Sodium intake while others experience almost no change. These differences are, in part, attributable to genetic variation in pathways involved in Sodium handling and excretion. ENaC (epithelial Sodium channel) is one of the key transporters responsible for the Reabsorption of Sodium in the distal nephron. This channel has an important role in the regulation of extracellular fluid volume and consequently blood pressure. Herein, we review the role of ENaC in the development of salt-sensitive hypertension, and present mechanistic insights into the regulation of ENaC activity and how it may accelerate Sodium-induced damage and dysfunction. We discuss the traditional role of ENaC in Renal Sodium Reabsorption and review work addressing ENaC expression and function in the brain, vasculature, and immune cells, and how this has expanded the implications for its role in the initiation and progression of salt-sensitive hypertension.
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Blood pressure and amiloride-sensitive Sodium channels in vascular and Renal cells
Nature Reviews Nephrology, 2014Co-Authors: David G. Warnock, Kristina Kusche-vihrog, Antoine Tarjus, Shaohu Sheng, Hans Oberleithner, Thomas R. Kleyman, Frederic JaisserAbstract:Renal perfusion pressure, glomerular filtration and net Renal Sodium Reabsorption maintain volume homeostasis Cell stiffness and myogenic tone contribute to peripheral vascular resistance in the presence of aldosterone and normal Sodium concentrations in the arterial circulation Structural similarities exist between the amiloride-sensitive Sodium channels in the epithelial and endothelial cells Distinctions based on functional differences, especially in response to changes in extracellular Sodium concentrations, might permit development of novel pharmacological approaches to differentially target epithelial and endothelial Sodium channels Agents that preferentially inhibit the vascular channels could lower systemic blood pressure without the associated inhibition of potassium secretion that accompanies the available Sodium channel blockers and mineralocorticoid receptor antagonists Blood pressure control is influenced by amiloride-sensitive Sodium channels in the vascular and epithelial homeostatic systems in the kidney. Here, the authors describe the expression and regulation of Sodium channels, and they outline the emerging evidence that differences between Sodium channel complexes expressed in the epithelia and endothelia might permit novel therapeutic approaches to lower systemic blood pressure without the adverse effects associated with the Sodium channel blockers that are currently available. Sodium transport in the distal nephron is mediated by epithelial Sodium channel activity. Proteolytic processing of external domains and inhibition with increased Sodium concentrations are important regulatory features of epithelial Sodium channel complexes expressed in the distal nephron. By contrast, Sodium channels expressed in the vascular system are activated by increased external Sodium concentrations, which results in changes in the mechanical properties and function of endothelial cells. Mechanosensitivity and shear stress affect both epithelial and vascular Sodium channel activity. Guyton's hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. The synergistic effects, and complementary regulation, of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and probably reflect sequential evolution of the two systems. The integration of vascular tone, Renal perfusion and regulation of Renal Sodium Reabsorption is the central underpinning of the Guytonian model. In this Review, we focus on the expression and regulation of Sodium channels, and we outline the emerging evidence that describes the central role of amiloride-sensitive Sodium channels in the efferent (vascular) and afferent (epithelial) arms of this homeostatic system.
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Blood pressure and amiloride-sensitive Sodium channels in vascular and Renal cells.
Nature reviews. Nephrology, 2014Co-Authors: David G. Warnock, Kristina Kusche-vihrog, Antoine Tarjus, Shaohu Sheng, Hans Oberleithner, Thomas R. Kleyman, Frederic JaisserAbstract:Sodium transport in the distal nephron is mediated by epithelial Sodium channel activity. Proteolytic processing of external domains and inhibition with increased Sodium concentrations are important regulatory features of epithelial Sodium channel complexes expressed in the distal nephron. By contrast, Sodium channels expressed in the vascular system are activated by increased external Sodium concentrations, which results in changes in the mechanical properties and function of endothelial cells. Mechanosensitivity and shear stress affect both epithelial and vascular Sodium channel activity. Guyton's hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. The synergistic effects, and complementary regulation, of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and probably reflect sequential evolution of the two systems. The integration of vascular tone, Renal perfusion and regulation of Renal Sodium Reabsorption is the central underpinning of the Guytonian model. In this Review, we focus on the expression and regulation of Sodium channels, and we outline the emerging evidence that describes the central role of amiloride-sensitive Sodium channels in the efferent (vascular) and afferent (epithelial) arms of this homeostatic system.
David G. Warnock - One of the best experts on this subject based on the ideXlab platform.
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Blood pressure and amiloride-sensitive Sodium channels in vascular and Renal cells
Nature Reviews Nephrology, 2014Co-Authors: David G. Warnock, Kristina Kusche-vihrog, Antoine Tarjus, Shaohu Sheng, Hans Oberleithner, Thomas R. Kleyman, Frederic JaisserAbstract:Renal perfusion pressure, glomerular filtration and net Renal Sodium Reabsorption maintain volume homeostasis Cell stiffness and myogenic tone contribute to peripheral vascular resistance in the presence of aldosterone and normal Sodium concentrations in the arterial circulation Structural similarities exist between the amiloride-sensitive Sodium channels in the epithelial and endothelial cells Distinctions based on functional differences, especially in response to changes in extracellular Sodium concentrations, might permit development of novel pharmacological approaches to differentially target epithelial and endothelial Sodium channels Agents that preferentially inhibit the vascular channels could lower systemic blood pressure without the associated inhibition of potassium secretion that accompanies the available Sodium channel blockers and mineralocorticoid receptor antagonists Blood pressure control is influenced by amiloride-sensitive Sodium channels in the vascular and epithelial homeostatic systems in the kidney. Here, the authors describe the expression and regulation of Sodium channels, and they outline the emerging evidence that differences between Sodium channel complexes expressed in the epithelia and endothelia might permit novel therapeutic approaches to lower systemic blood pressure without the adverse effects associated with the Sodium channel blockers that are currently available. Sodium transport in the distal nephron is mediated by epithelial Sodium channel activity. Proteolytic processing of external domains and inhibition with increased Sodium concentrations are important regulatory features of epithelial Sodium channel complexes expressed in the distal nephron. By contrast, Sodium channels expressed in the vascular system are activated by increased external Sodium concentrations, which results in changes in the mechanical properties and function of endothelial cells. Mechanosensitivity and shear stress affect both epithelial and vascular Sodium channel activity. Guyton's hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. The synergistic effects, and complementary regulation, of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and probably reflect sequential evolution of the two systems. The integration of vascular tone, Renal perfusion and regulation of Renal Sodium Reabsorption is the central underpinning of the Guytonian model. In this Review, we focus on the expression and regulation of Sodium channels, and we outline the emerging evidence that describes the central role of amiloride-sensitive Sodium channels in the efferent (vascular) and afferent (epithelial) arms of this homeostatic system.
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Blood pressure and amiloride-sensitive Sodium channels in vascular and Renal cells.
Nature reviews. Nephrology, 2014Co-Authors: David G. Warnock, Kristina Kusche-vihrog, Antoine Tarjus, Shaohu Sheng, Hans Oberleithner, Thomas R. Kleyman, Frederic JaisserAbstract:Sodium transport in the distal nephron is mediated by epithelial Sodium channel activity. Proteolytic processing of external domains and inhibition with increased Sodium concentrations are important regulatory features of epithelial Sodium channel complexes expressed in the distal nephron. By contrast, Sodium channels expressed in the vascular system are activated by increased external Sodium concentrations, which results in changes in the mechanical properties and function of endothelial cells. Mechanosensitivity and shear stress affect both epithelial and vascular Sodium channel activity. Guyton's hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. The synergistic effects, and complementary regulation, of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and probably reflect sequential evolution of the two systems. The integration of vascular tone, Renal perfusion and regulation of Renal Sodium Reabsorption is the central underpinning of the Guytonian model. In this Review, we focus on the expression and regulation of Sodium channels, and we outline the emerging evidence that describes the central role of amiloride-sensitive Sodium channels in the efferent (vascular) and afferent (epithelial) arms of this homeostatic system.
John E. Hall - One of the best experts on this subject based on the ideXlab platform.
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Obesity and Metabolic Syndrome Hypertension
Updates in Hypertension and Cardiovascular Protection, 2018Co-Authors: Michael E. Hall, Jussara M. Do Carmo, Zhen Wang, Daisuke Kamimura, John E. HallAbstract:Obesity is a growing problem worldwide, and excess visceral adiposity is a major risk factor for many metabolic, kidney, and cardiovascular disorders including primary (essential) hypertension. The mechanisms by which obesity leads to hypertension and kidney dysfunction are not completely understood, but physical compression of the kidneys and activation of the renin-angiotensin-aldosterone and sympathetic nervous systems appear to initially increase Renal Sodium Reabsorption, impair Renal-pressure natriuresis, and ultimately raise blood pressure. Other factors such as lipotoxicity and endothelial and vascular dysfunction may accompany and/or exacerbate increased blood pressure as obesity is sustained. Concomitant vascular and metabolic derangements such as hyperglycemia and inflammation interact with increased blood pressure to cause kidney injury which exacerbates the hypertension, making it more difficult to control while causing further Renal injury. Maintenance of a healthy weight is important for primary prevention of hypertension and kidney disease. Weight loss, if it can be achieved, appears to be effective in treating many patients with chronic hypertension and kidney disease. However, long-term weight management is challenging for many people, and more effective therapeutic options are needed.
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obesity induced hypertension role of sympathetic nervous system leptin and melanocortins
Journal of Biological Chemistry, 2010Co-Authors: John E. Hall, Alexandre A. Da Silva, Jussara Do M Carmo, Joh H Dubinio, Sheree M Hamza, Shanka Munusamy, Gra Smith, David E StecAbstract:Excess weight gain contributes to increased blood pressure in most patients with essential hypertension. Although the mechanisms of obesity hypertension are not fully understood, increased Renal Sodium Reabsorption and impaired pressure natriuresis play key roles. Several mechanisms contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system, which appears to be mediated in part by increased levels of the adipocyte-derived hormone leptin, stimulation of pro-opiomelanocortin neurons, and subsequent activation of central nervous system melanocortin 4 receptors.
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The role of the sympathetic nervous system in obesity-related hypertension.
Current Hypertension Reports, 2009Co-Authors: Alexandre A. Da Silva, Jussara M. Do Carmo, John H. Dubinion, John E. HallAbstract:Obesity is recognized as a major health problem throughout the world. Excess weight is a major cause of increased blood pressure in most patients with essential hypertension and greatly increases the risk for diabetes, cardiovascular diseases, and end-stage Renal disease. Although the mechanisms by which obesity raises blood pressure are not completely understood, increased Renal Sodium Reabsorption, impaired pressure natriuresis, and volume expansion appear to play important roles. Several potential mechanisms have been suggested to contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, as well as physical compression of the kidneys, especially when visceral obesity is present. Activation of the sympathetic nervous system in obesity may be due, in part, to hyperleptinemia and other factors secreted by adipocytes and the gastrointestinal tract, activation of the central nervous system melanocortin pathway, and baroreceptor dysfunction.
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Pathophysiology of obesity hypertension.
Current hypertension reports, 2000Co-Authors: John E. HallAbstract:Excess weight gain is a major cause of essential hypertension, and abnormal kidney function appears to be a cause as well as a consequence of obesity hypertension. Excess Renal Sodium Reabsorption and a hypertensive shift of pressure natriuresis play a major role in mediating increased blood pressure associated with weight gain. Activation of the renin-angiotensin and sympathetic nervous systems and physical compression of the kidneys appear to contribute to obesity-induced increases in Sodium Reabsorption and hypertension.
Ryu Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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deletion of the angiotensin ii type 1 receptor associated protein enhances Renal Sodium Reabsorption and exacerbates angiotensin ii mediated hypertension
Kidney International, 2014Co-Authors: Masato Ohsawa, Kouichi Tamura, Hiromichi Wakui, Akinobu Maeda, Toru Dejima, Tomohiko Kanaoka, Kengo Azushima, Kazushi Uneda, Yuko Tsurumiikeya, Ryu KobayashiAbstract:Angiotensin II type 1 receptor (AT1R)–associated protein (ATRAP) promotes AT1R internalization along with suppression of pathological activation of tissue AT1R signaling. However, the functional significance of ATRAP in Renal Sodium handling and blood pressure regulation under pathological stimuli is not fully resolved. Here we show the blood pressure of mice with a gene-targeted disruption of ATRAP was comparable to that of wild-type mice at baseline. However, in ATRAP-knockout mice, angiotensin II–induced hypertension was exacerbated and the extent of positive Sodium balance was increased by angiotensin II. Renal expression of the Sodium-proton antiporter 3, a major Sodium transporter in the proximal tubules, urinary pH, Renal angiotensinogen production, and angiotensin II content was unaffected. Stimulation of the Renal expression and activity of the epithelial Sodium channel (ENaC), a major Sodium transporter in the distal tubules, was significantly enhanced by chronic angiotensin II infusion. The circulating and urinary aldosterone levels were comparable. The blood pressure response and Renal ENaC expression by aldosterone were not affected. Thus, ATRAP deficiency exacerbated angiotensin II–mediated hypertension by pathological activation of Renal tubular AT1R by angiotensin II. This directly stimulates ENaC in the distal tubules and enhances Sodium retention in an aldosterone-independent manner.
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Deletion of the angiotensin II type 1 receptor–associated protein enhances Renal Sodium Reabsorption and exacerbates angiotensin II–mediated hypertension
Kidney international, 2014Co-Authors: Masato Ohsawa, Kouichi Tamura, Hiromichi Wakui, Akinobu Maeda, Toru Dejima, Tomohiko Kanaoka, Kengo Azushima, Kazushi Uneda, Yuko Tsurumi-ikeya, Ryu KobayashiAbstract:Angiotensin II type 1 receptor (AT1R)–associated protein (ATRAP) promotes AT1R internalization along with suppression of pathological activation of tissue AT1R signaling. However, the functional significance of ATRAP in Renal Sodium handling and blood pressure regulation under pathological stimuli is not fully resolved. Here we show the blood pressure of mice with a gene-targeted disruption of ATRAP was comparable to that of wild-type mice at baseline. However, in ATRAP-knockout mice, angiotensin II–induced hypertension was exacerbated and the extent of positive Sodium balance was increased by angiotensin II. Renal expression of the Sodium-proton antiporter 3, a major Sodium transporter in the proximal tubules, urinary pH, Renal angiotensinogen production, and angiotensin II content was unaffected. Stimulation of the Renal expression and activity of the epithelial Sodium channel (ENaC), a major Sodium transporter in the distal tubules, was significantly enhanced by chronic angiotensin II infusion. The circulating and urinary aldosterone levels were comparable. The blood pressure response and Renal ENaC expression by aldosterone were not affected. Thus, ATRAP deficiency exacerbated angiotensin II–mediated hypertension by pathological activation of Renal tubular AT1R by angiotensin II. This directly stimulates ENaC in the distal tubules and enhances Sodium retention in an aldosterone-independent manner.