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Thomas M Coffman - One of the best experts on this subject based on the ideXlab platform.

  • vascular type 1a angiotensin ii receptors control bp by regulating Renal blood flow and urinary sodium excretion
    Journal of The American Society of Nephrology, 2015
    Co-Authors: Matthew A Sparks, Johannes Stegbauer, Daian Chen, Jose A Gomez, Robert Griffiths, Hooman A Azad, Marcela Herrera, Susan B Gurley, Thomas M Coffman
    Abstract:

    Inappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II-dependent responses in the Renal Circulation were almost completely eliminated in SMKO mice (approximately 5%-10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of Renal blood flow by Ang II and highlight the capacity of Ang II-dependent vascular responses in the kidney to effect natriuresis and BP control.

Rinaldo Bellomo - One of the best experts on this subject based on the ideXlab platform.

  • sepsis associated acute kidney injury macrohemodynamic and microhemodynamic alterations in the Renal Circulation
    Seminars in Nephrology, 2015
    Co-Authors: John R Prowle, Rinaldo Bellomo
    Abstract:

    Summary Traditionally, Renal ischemia has been regarded as central to the pathogenesis of sepsis-associated acute kidney injury (SA-AKI). Accordingly, hemodynamic management of SA-AKI has emphasized restoration of Renal perfusion, whereas, experimentally, ischemia reperfusion models have been emphasized. However, in human beings, SA-AKI usually is accompanied by hyperdynamic Circulation. Moreover, clinical and experimental evidence now suggests the importance of inflammatory mechanisms in the development of AKI and microcirculatory dysfunction more than systemic alteration in Renal perfusion. In this review, we examine systemic, regional, and microcirculatory hemodynamics in SA-AKI, and attempt to rationalize the hemodynamic management of this condition.

  • c urrent opinion Renal blood flow fractional excretion of sodium and acute kidney injury time for a new paradigm
    2012
    Co-Authors: John R Prowle, Sean M Bagshaw, Rinaldo Bellomo
    Abstract:

    Purpose of reviewGlobal Renal blood flow is considered pivotal to Renal function. Decreased global Renal blood flow(decreased perfusion) is further considered the major mechanism of reduced glomerular filtration rateresponsible for the development of acute kidney injury (AKI) in critically ill patients. Additionally, urinarybiochemical tests are widely taught to allow the differential diagnosis of preRenal (functional) AKI andintrinsic [structural AKI (so-called acute tubular necrosis)]. In this review we will examine recent evidenceregarding these two key clinical paradigms.Recent findingsRecent animal experiments and clinical studies in humans using cine-phase contrast magnetic resonancetechnology are not consistent with the decreased perfusion paradigm. They suggest instead that changes inthe intra-Renal Circulation including modification in efferent arteriolar function and intra-Renal shunting aremuch more likely to be responsible for AKI, especially in sepsis. Similarly, recent human studies indicatethe urinary biochemistry has limited diagnostic or prognostic ability and is dissociated form biomarker andmicroscopic evidence of tubular injury.SummaryIntra-Renal microcirculatory changes are likely more important than changes in global blood flow in thedevelopment of AKI. Urinary biochemistry is not a clinically useful diagnostic or prognostic tool in criticallyill patients at risk of or with AKI.Keywordsacute kidney injury, fractional excretion of sodium, fractional excretion of urea, Renal blood flow, urinalysis

Gary G Gibbs - One of the best experts on this subject based on the ideXlab platform.

  • modulation of Renal cortical blood flow during static exercise in humans
    Circulation Research, 1997
    Co-Authors: Holly R Middlekauff, Egbert U Nitzsche, Alison H Nguyen, Carl K Hoh, Gary G Gibbs
    Abstract:

    During static exercise, several reflex systems that increase sympathetic nerve activity, heart rate, arterial pressure, and cardiac output are activated. At rest, the Renal Circulation receives the most blood flow per tissue weight of any organ in the body. However, the Renal circulatory response to static exercise has not been studied in humans because of technical limitations in methods for measuring rapid changes in Renal blood flow. The aim of this study was to determine the Renal blood flow response to static exercise in healthy humans and, specifically, to clarify the reflex mechanisms underlying this response. Renal cortical blood flow was measured using dynamic positron emission tomography and the blood flow agent oxygen-15 water. Graded handgrip exercise, posthandgrip circulatory arrest, and administration of intra-arterial adenosine were performed to clarify the mechanisms controlling Renal blood flow during static exercise. The major new findings in this study are that in healthy humans (1) ren...

Stephen C. Textor - One of the best experts on this subject based on the ideXlab platform.

  • blood oxygen level dependent bold mri in renovascular hypertension
    Current Hypertension Reports, 2011
    Co-Authors: Monika L Gloviczki, Lilach O. Lerman, Stephen C. Textor
    Abstract:

    Establishing whether large vessel occlusive disease threatens tissue oxygenation and viability in the post-stenotic kidney is difficult for clinicians. Development of blood oxygen level–dependent (BOLD) MRI methods can allow functional evaluation of regional differences in deoxyhemoglobin levels within the kidney without requiring contrast. The complex Renal Circulation normally provides a gradient of oxygenation from a highly vascular cortex to much reduced levels in the deep sections of medulla, dependent upon adjustments in Renal afferent arterioles, oxygen consumption related to solute transport, and arteriovenous shunting related to the juxtaposition of descending and ascending vasa recta. Studies with BOLD imaging have identified adaptation to substantial reductions in Renal blood flow, volume, and glomerular filtration rate in post-stenotic kidneys that preserves medullary and cortical oxygenation during medical therapy. However, extreme vascular compromise overwhelms these adaptive changes and leads to cortical hypoxia and microvascular injury.

  • renovascular hypertension and ischemic nephropathy
    Circulation, 2005
    Co-Authors: Vesna D Garovic, Stephen C. Textor
    Abstract:

    Major improvements in imaging, medical therapy, and techniques of Renal revascularization have changed the landscape of renovascular disease during the past decade. This has been particularly true for atherosclerotic Renal artery stenosis, which remains one of the most common conditions known to accelerate hypertension and one of the most common incidentally detected vascular lesions. Despite, or perhaps because of, these developments, few clinical questions provoke more controversy and debate among cardiologists, internists, and nephrologists than decisions about the optimal management of patients with main Renal artery stenosis. Even well-informed clinicians from different subspecialties hold widely divergent opinions about the role of Renal revascularization, particularly for atherosclerotic disease. Studies of Medicare claims data indicate that application of peripheral intervention procedures varies >14-fold between various parts of the country.1 Some of those from interventional subspecialties (primarily interventional radiology and cardiology) emphasize the major benefits now available from endovascular procedures, including the use of stents. They argue that revascularization offers the potential to improve or reverse renovascular hypertension, to salvage or preserve the Renal Circulation and Renal function, and to improve the management of patients with refractory forms of congestive heart failure.2 A recent review of the use of percutaneous Renal artery procedures among Medicare beneficiaries confirms a rise from 7660 claims in 1996 to 18 520 claims in 2000, primarily because of a 2.8-fold increase in procedures by interventional cardiologists.3 Many in the nephrology community review the same published literature and reach nearly opposite conclusions. They argue that recent prospective studies fail to reveal major benefits of blood pressure control related to Renal revascularization, that the risks of complications from interventional procedures are substantial, including uncommon but sometimes devastating loss of Renal function resulting from atheroembolic disease.4 Despite a wave of enthusiasm in the early 1990s to identify …

Natalia Alenina - One of the best experts on this subject based on the ideXlab platform.

  • stretch activation of angiotensin ii type 1a receptors contributes to the myogenic response of mouse mesenteric and Renal arteries
    Circulation Research, 2014
    Co-Authors: Johanna Schleifenbaum, Jean-yves Tano, Mario Kassmann, Istvan Andras Szijarto, Hantz C Hercule, Stefanie Weinert, Matthias Heidenreich, Asif R Pathan, Yolandmarie Anistan, Natalia Alenina
    Abstract:

    Rationale: Vascular wall stretch is the major stimulus for the myogenic response of small arteries to pressure. The molecular mechanisms are elusive, but recent findings suggest that G protein–coupled receptors can elicit a stretch response. Objective: To determine whether angiotensin II type 1 receptors (AT 1 R) in vascular smooth muscle cells exert mechanosensitivity and identify the downstream ion channel mediators of myogenic vasoconstriction. Methods and Results: We used mice deficient in AT 1 R signaling molecules and putative ion channel targets, namely AT 1 R, angiotensinogen, transient receptor potential channel 6 (TRPC6) channels, or several subtypes of the voltage-gated K + (K v 7) gene family (KCNQ3, 4, or 5). We identified a mechanosensing mechanism in isolated mesenteric arteries and in the Renal Circulation that relies on coupling of the AT 1 R subtype a to a G q/11 protein as a critical event to accomplish the myogenic response. Arterial mechanoactivation occurs after pharmacological block of AT 1 R and in the absence of angiotensinogen or TRPC6 channels. Activation of AT 1 R subtype a by osmotically induced membrane stretch suppresses an XE991-sensitive K v channel current in patch-clamped vascular smooth muscle cells, and similar concentrations of XE991 enhance mesenteric and Renal myogenic tone. Although XE991-sensitive KCNQ3, 4, and 5 channels are expressed in vascular smooth muscle cells, XE991-sensitive K + current and myogenic contractions persist in arteries deficient in these channels. Conclusions: Our results provide definitive evidence that myogenic responses of mouse mesenteric and Renal arteries rely on ligand-independent, mechanoactivation of AT 1 R subtype a. The AT 1 R subtype a signal relies on an ion channel distinct from TRPC6 or KCNQ3, 4, or 5 to enact vascular smooth muscle cell activation and elevated vascular resistance.