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Pflugers Archiv : European Journal of... Aug 2022Our kidneys receive about one-fifth of the cardiac output at rest and have a low oxygen extraction ratio, but may sustain, under some conditions, hypoxic injuries that... (Review)
Review
Our kidneys receive about one-fifth of the cardiac output at rest and have a low oxygen extraction ratio, but may sustain, under some conditions, hypoxic injuries that might lead to chronic kidney disease. This is due to large regional variations in renal blood flow and oxygenation, which are the prerequisite for some and the consequence of other kidney functions. The concurrent operation of these functions is reliant on a multitude of neuro-hormonal signaling cascades and feedback loops that also include the regulation of renal blood flow and tissue oxygenation. Starting with open questions on regulatory processes and disease mechanisms, we review herein the literature on renal blood flow and oxygenation. We assess the current understanding of renal blood flow regulation, reasons for disparities in oxygen delivery and consumption, and the consequences of disbalance between O delivery, consumption, and removal. We further consider methods for measuring and computing blood velocity, flow rate, oxygen partial pressure, and related parameters and point out how limitations of these methods constitute important hurdles in this area of research. We conclude that to obtain an integrated understanding of the relation between renal function and renal blood flow and oxygenation, combined experimental and computational modeling studies will be needed.
Topics: Humans; Hypoxia; Kidney; Oxygen; Oxygen Consumption; Renal Circulation
PubMed: 35438336
DOI: 10.1007/s00424-022-02690-y -
Physiological Research Jul 2020Proper renal blood flow (RBF) and glomerular filtration rate (GFR) are critical for maintaining normal blood pressure, kidney function and water and electrolyte... (Review)
Review
Proper renal blood flow (RBF) and glomerular filtration rate (GFR) are critical for maintaining normal blood pressure, kidney function and water and electrolyte homeostasis. The renal microvasculature expresses a multitude of receptors mediating vasodilation and vasoconstriction, which can influence glomerular blood flow and capillary pressure. Despite this, RBF and GFR remain quite stable when arterial pressure fluctuates because of the autoregulatory mechanism. ATP and adenosine participate in autoregulatory control of RBF and GFR via activation of two different purinoceptor families (P1 and P2). Purinoceptors are widely expressed in renal microvasculature and tubules. Emerging data show altered purinoceptor signaling in hypertension-associated kidney injury, diabetic nephropathy, sepsis, ischemia-reperfusion induced acute kidney injury and polycystic kidney disease. In this brief review, we highlight recent studies and new insights on purinoceptors regulating renal microvascular function and renal hemodynamics. We also address the mechanisms underlying renal microvascular injury and impaired renal autoregulation, focusing on purinoceptor signaling and hypertension-induced renal microvascular dysfunction. Interested readers are directed to several excellent and comprehensive reviews that recently covered the topics of renal autoregulation, and nucleotides in kidney function under physiological and pathophysiological conditions (Inscho 2009, Navar et al. 2008, Carlstrom et al. 2015, Vallon et al. 2020).
Topics: Animals; Glomerular Filtration Rate; Homeostasis; Humans; Hypertension; Kidney; Receptors, Purinergic; Renal Circulation
PubMed: 32301620
DOI: 10.33549/physiolres.934463 -
Seminars in Nephrology Mar 2015Endothelin (ET) is one of the most potent renal vasoconstrictors. Endothelin plays an essential role in the regulation of renal blood flow, glomerular filtration, sodium... (Review)
Review
Endothelin (ET) is one of the most potent renal vasoconstrictors. Endothelin plays an essential role in the regulation of renal blood flow, glomerular filtration, sodium and water transport, and acid-base balance. ET-1, ET-2, and ET-3 are the three distinct endothelin isoforms comprising the endothelin family. ET-1 is the major physiologically relevant peptide and exerts its biological activity through two G-protein-coupled receptors: ET(A) and ET(B). Both ET(A) and ET(B) are expressed by the renal vasculature. Although ET(A) are expressed mainly by vascular smooth muscle cells, ET(B) are expressed by both renal endothelial and vascular smooth muscle cells. Activation of the endothelin system, or overexpression of downstream endothelin signaling pathways, has been implicated in several pathophysiological conditions including hypertension, acute kidney injury, diabetic nephropathy, and immune nephritis. In this review, we focus on the effects of endothelin on the renal microvasculature, and update recent findings on endothelin in the regulation of renal hemodynamics.
Topics: Endothelins; Glomerular Filtration Rate; Humans; Microcirculation; Renal Circulation
PubMed: 25966346
DOI: 10.1016/j.semnephrol.2015.02.004 -
Journal of the American Society of... Apr 2019
Topics: Hand Strength; Humans; Kidney Cortex; Magnetic Resonance Imaging; Perfusion; Renal Circulation
PubMed: 30760497
DOI: 10.1681/ASN.2019010049 -
American Journal of Physiology. Renal... May 2014During the first trimester of human pregnancy, the maternal systemic circulation undergoes remarkable vasodilation. The kidneys participate in this vasodilatory response... (Comparative Study)
Comparative Study Review
During the first trimester of human pregnancy, the maternal systemic circulation undergoes remarkable vasodilation. The kidneys participate in this vasodilatory response resulting in marked increases in renal plasma flow (RPF) and glomerular filtration rate (GFR). Comparable circulatory adaptations are observed in conscious gravid rats. Administration of the corpus luteal hormone relaxin (RLN) to nonpregnant rats and humans elicits vasodilatory changes like those of pregnancy. Systemic and renal vasodilation are compromised in midterm pregnant rats by neutralization or elimination of circulating RLN and in women conceiving with donor eggs who lack a corpus luteum and circulating RLN. Although RLN exerts both rapid (minutes) and sustained (hours to days) vasodilatory actions through different molecular mechanisms, a final common pathway is endothelial nitric oxide. In preeclampsia (PE), maternal systemic and renal vasoconstriction leads to hypertension and modest reduction in GFR exceeding that of RPF. Elevated level of circulating soluble vascular endothelial growth factor receptor-1 arising from the placenta is implicated in the hypertension and disruption of glomerular fenestrae and barrier function, the former causing reduced Kf and the latter proteinuria. Additional pathogenic factors are discussed. Last, potential clinical ramifications include RLN replacement in women conceiving with donor eggs and its therapeutic use in PE. Another goal has been to apply knowledge gained from investigating circulatory adaptations in pregnancy toward identifying and developing novel therapeutic strategies for renal and cardiovascular disease in the nonpregnant population. So far, one candidate to emerge is RLN and its potential therapeutic use in heart failure.
Topics: Animals; Female; Glomerular Filtration Rate; Humans; Kidney; Models, Animal; Pre-Eclampsia; Pregnancy; Pregnancy, Animal; Rats; Regional Blood Flow; Relaxin; Renal Circulation; Renal Plasma Flow; Vasodilation
PubMed: 24647709
DOI: 10.1152/ajprenal.00042.2014 -
American Journal of Physiology. Renal... Oct 2018Renovascular disease (RVD), which is prevalent in the elderly, significantly increases cardiovascular risk and can progressively deteriorate renal function. The loss of... (Review)
Review
Renovascular disease (RVD), which is prevalent in the elderly, significantly increases cardiovascular risk and can progressively deteriorate renal function. The loss of renal function in patients with RVD is associated with a progressive dysfunction, damage, and loss of renal microvessels, which can be combined with decreased renal bioavailability of vascular endothelial growth factor (VEGF) and a defective vascular repair and proliferation. This association has been the impetus for recent efforts that have focused on developing methods to stop the progression of renal injury by protecting the renal microvasculature. This mini-review focuses on recent studies supporting potential applications of VEGF therapy for the kidney and discusses underlying mechanisms of renoprotection.
Topics: Animals; Humans; Kidney; Neovascularization, Physiologic; Renal Artery Obstruction; Renal Circulation; Vascular Endothelial Growth Factor A
PubMed: 29442546
DOI: 10.1152/ajprenal.00617.2017 -
Critical Care (London, England) Mar 2018The importance of personalized blood pressure management is well recognized. Because renal pressure-flow relationships may vary among patients, understanding how renal... (Review)
Review
The importance of personalized blood pressure management is well recognized. Because renal pressure-flow relationships may vary among patients, understanding how renal autoregulation may influence blood pressure control is essential. However, much remains uncertain regarding the determinants of renal autoregulation in circulatory shock, including the influence of comorbidities and the effects of vasopressor treatment. We review published studies on renal autoregulation relevant to the management of acutely ill patients with shock. We delineate the main signaling pathways of renal autoregulation, discuss how it can be assessed, and describe the renal autoregulatory alterations associated with chronic disease and with shock.
Topics: Animals; Blood Pressure; Disease Models, Animal; Dogs; Homeostasis; Kidney; Mice; Renal Circulation; Shock; Swine; Vasoconstrictor Agents
PubMed: 29566705
DOI: 10.1186/s13054-018-1962-8 -
Journal of the American Society of... Jun 2021To perform their functions, the kidneys maintain stable blood perfusion in the face of fluctuations in systemic BP. This is done through autoregulation of blood flow by... (Review)
Review
To perform their functions, the kidneys maintain stable blood perfusion in the face of fluctuations in systemic BP. This is done through autoregulation of blood flow by the generic myogenic response and the kidney-specific tubuloglomerular feedback (TGF) mechanism. The central theme of this paper is that, to achieve autoregulation, nephrons do not work as single units to manage their individual blood flows, but rather communicate electrically over long distances to other nephrons the vascular tree. Accordingly, we define the nephrovascular unit (NVU) to be a structure consisting of the nephron, glomerulus, afferent arteriole, and efferent arteriole. We discuss features that require and enable distributed autoregulation mediated by TGF across the kidney. These features include the highly variable topology of the renal vasculature which creates variability in circulation and the potential for mismatch between tubular oxygen demand and delivery; the self-sustained oscillations in each NVU arising from the autoregulatory mechanisms; and the presence of extensive gap junctions formed by connexins and their properties that enable long-distance transmission of TGF signals. The existence of TGF synchronization across the renal microvascular network enables an understanding of how NVUs optimize oxygenation-perfusion matching while preventing transmission of high systemic pressure to the glomeruli, which could lead to progressive glomerular and vascular injury.
Topics: Animals; Arterioles; Blood Pressure; Connexins; Feedback, Physiological; Homeostasis; Humans; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Nephrons; Renal Circulation; Signal Transduction
PubMed: 33833078
DOI: 10.1681/ASN.2020040423 -
European Review For Medical and... 2016The purpose of the study is to further investigate the effects of increased intra-abdominal pressure (IAP) on renal hemodynamics and renal perfusion, and to evaluate the...
OBJECTIVE
The purpose of the study is to further investigate the effects of increased intra-abdominal pressure (IAP) on renal hemodynamics and renal perfusion, and to evaluate the renal cortical and sublingual microcirculation by sidestream dark field (SDF) imaging, both with a porcine model.
MATERIALS AND METHODS
IAP was increased stepwise to 10, 15, 20, 25 mmHg, during which hemodynamic parameters, urinary output, renal contrast-enhanced ultrasound (CEUS), sublingual and renal SDF videos were all recorded from 12 pigs.
RESULTS
Wash in time (WT) and time to peak (TTP) prolonged significantly (p<0.05), while peak intensity (PI) wash in slope (WS) and AUC (area under curve) in CEUS declined significantly (p<0.05) compared with baseline when IAP elevated to 25 mm Hg. With an increase of abdominal pressure, sublingual microvascular flow index (MFI) drop significantly, especially upon IAP was over 20 mmHg. But other parameters such as the total vascular density (TVD), De Backer Score, proportion of perfused vessels (PPV), perfused vessel density (PVD), and heterogeneity index (HI) of tongue were not significantly changed. With increasing IAP, renal vascular resistance increased and MFI decreased about 30%. RFG, instead of RFG showed a moderate correlation with AUC (R=0.47, p<0.05) and MFI (R=0.49, p<0.05).
CONCLUSIONS
CEUS is a safe, real-time dynamic, noninvasive and simple technique to evaluate renal microvascular perfusion in intra-abdominal hypertension. Descending slope, PI and AUC can be used for the diagnosis of the renal microvascular damage in a porcine model of IAP-induced renal impairment. Also, SDF on the surface of the kidney is a useful tool to evaluate the microcirculation of kidney but sublingual SDF imaging was barely useful.
Topics: Animals; Contrast Media; Disease Models, Animal; Hemodynamics; Intra-Abdominal Hypertension; Kidney; Kidney Cortex; Microcirculation; Renal Circulation; Swine; Vascular Resistance
PubMed: 26914119
DOI: No ID Found -
Physiological Reports Mar 2023The present study was to examine sex and strain differences in glomerular filtration rate (GFR) and renal blood flow (RBF) in C57BL6, 129/Sv, and C57BLKS/J mice, three...
The present study was to examine sex and strain differences in glomerular filtration rate (GFR) and renal blood flow (RBF) in C57BL6, 129/Sv, and C57BLKS/J mice, three commonly used mouse strains in renal research. GFR was measured by transdermal measurement of FITC-sinitrin clearance in conscious mice. RBF was measured by a flow probe placed in the renal artery under an anesthetic state. In C57BL6 mice, there were no sex differences in both GFR and RBF. In 129/Sv mice, females had significantly greater GFR than males at age of 24 weeks, but not at 8 weeks. However, males had higher RBF and lower renal vascular resistance (RVR). Similar to 129/Sv, female C57BLKS/J had significantly greater GFR at both 8 and 24 weeks, lower RBF, and higher RVR than males. Across strains, male 129/Sv had lower GFR and higher RBF than male C57BL6, but no significant difference in GFR and greater RBF than male C57BLKS/J. No significant difference in GFR or RBF was observed between C57BL6 and C57BLKS/J mice. Deletion of eNOS in C57BLKS/J mice reduced GFR in both sexes, but decreased RBF in males. Furthermore, there were no sex differences in the severity of renal injury in eNOS dbdb mice. Taken together, our study suggests that sex differences in renal hemodynamics in mice are strain and age dependent. eNOS was not involved in the sex differences in GFR, but in RBF. Furthermore, the sexual dimorphism did not impact the severity of renal injury in diabetic nephropathy.
Topics: Mice; Male; Animals; Female; Mice, Inbred C57BL; Kidney; Hemodynamics; Renal Circulation; Vascular Resistance; Glomerular Filtration Rate
PubMed: 36946063
DOI: 10.14814/phy2.15644