scholarly journals Dynamic myogenic autoregulation in the rat kidney: a whole-organ model

2008 ◽  
Vol 294 (6) ◽  
pp. F1453-F1464 ◽  
Author(s):  
N. Kleinstreuer ◽  
T. David ◽  
M. J. Plank ◽  
Z. Endre
Keyword(s):  
Mathematical Model ◽  
Rat Kidney ◽  
Morphological Data ◽  
Myogenic Response ◽  
Wall Tension ◽  
Renal Vasculature ◽  
Renal Autoregulation ◽  
Organ Model ◽  
Endothelial Nitric Oxide

A transient 1D mathematical model of whole-organ renal autoregulation in the rat is presented, examining the myogenic response on multiple levels of the renal vasculature. Morphological data derived from micro-CT imaging were employed to divide the vasculature via a Strahler ordering scheme. A previously published model of the myogenic response based on wall tension is expanded and adapted to fit the response of each level, corresponding to a distally dominant resistance distribution with the highest contributions localized to the afferent arterioles and interlobular arteries. The mathematical model was further developed to include the effects of in vivo viscosity variation and flow-induced dilation via endothelial nitric oxide production. Computer simulations of the autoregulatory response to pressure perturbations were examined and compared with experimental data. The model supports the hypothesis that change in circumferential wall tension is the catalyst for the myogenic response. The model provides a basis for examining the steady state and transient characteristics of the whole-organ renal myogenic response in the rat, as well as the modulatory influences of metabolic and hemodynamic factors.

scholarly journals Renal Autoregulation in Health and Disease

2015 ◽  
Vol 95 (2) ◽  
pp. 405-511 ◽  
Author(s):  
Mattias Carlström ◽  
Christopher S. Wilcox ◽  
William J. Arendshorst
Keyword(s):  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Tubuloglomerular Feedback ◽  
Free Calcium ◽  
Myogenic Response ◽  
Renal Vasculature ◽  
Renal Autoregulation ◽  
Positive Balance ◽  
Health And Disease

Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80–180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca2+]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca2+]ioccurs predominantly by Ca2+influx through L-type voltage-operated Ca2+channels (VOCC). Increased [Ca2+]iactivates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca2+from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca2+sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.

scholarly journals Aging Impairs Renal Autoregulation in Mice

Hypertension ◽  
2020 ◽  
Vol 75 (2) ◽  
pp. 405-412 ◽  
Author(s):  
Jin Wei ◽  
Jinxiu Zhu ◽  
Jie Zhang ◽  
Shan Jiang ◽  
Larry Qu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Tubuloglomerular Feedback ◽  
Myogenic Response ◽  
Renal Autoregulation ◽  
Integrin Α5 ◽  
Aging Kidney

Impaired renal autoregulation permits more transmission of disturbance in systemic blood pressure, which initiates barotrauma in intrarenal microvasculatures such as glomerular and tubulointerstitial capillaries, contributing to the development of kidney damage and deterioration in renal function, especially under the conditions with high blood pressure. Although it has been postulated that autoregulatory efficiency is attenuated in the aging kidney, direct evidence remains lacking. In the present study, we measured the autoregulation of renal blood flow, myogenic response of afferent arteriole (Af-Art), tubuloglomerular feedback in vivo with micropuncture, as well as tubuloglomerular feedback in vitro in isolated perfused juxtaglomerular apparatus in young and aged C57BL/6 mice. We found that renal blood flow was not significantly changed in response to a defined elevation of renal arterial pressure in young mice but significantly increased in aged mice. Additionally, myogenic response of Af-Art measured by microperfusion with a stepwise increase in perfusion pressure was significantly blunted in the aging kidney, which is associated with the attenuation of intraluminal pressure-induced intracellular calcium increases, as well as the reduced expression of integrin α5 (Itga5) in Af-Art. Moreover, both tubuloglomerular feedback in vivo and in vitro were nearly inactive in the aging kidney, which is associated with the significantly reduced expression of adenosine A1 receptor (A1AR) and suppressed vasoconstrictor response to adenosine in Af-Art. In conclusion, this study demonstrates that aging impairs renal autoregulation with blunted myogenic response and inhibited tubuloglomerular feedback response. The underlying mechanisms involve the downregulations of integrin α5 and A1AR in the Af-Art.

scholarly journals A mathematical model of the myogenic response to systolic pressure in the afferent arteriole

2011 ◽  
Vol 300 (3) ◽  
pp. F669-F681 ◽  
Author(s):  
Jing Chen ◽  
Ioannis Sgouralis ◽  
Leon C. Moore ◽  
Harold E. Layton ◽  
Anita T. Layton
Keyword(s):  
Blood Pressure ◽  
Mathematical Model ◽  
Systolic Blood Pressure ◽  
Rat Kidney ◽  
Systolic Pressure ◽  
Vessel Diameter ◽  
Renal Diseases ◽  
Myogenic Response ◽  
Afferent Arteriole

Elevations in systolic blood pressure are believed to be closely linked to the pathogenesis and progression of renal diseases. It has been hypothesized that the afferent arteriole (AA) protects the glomerulus from the damaging effects of hypertension by sensing increases in systolic blood pressure and responding with a compensatory vasoconstriction (Loutzenhiser R, Bidani A, Chilton L. Circ Res 90: 1316–1324, 2002). To investigate this hypothesis, we developed a mathematical model of the myogenic response of an AA wall, based on an arteriole model (Gonzalez-Fernandez JM, Ermentrout B. Math Biosci 119: 127–167, 1994). The model incorporates ionic transport, cell membrane potential, contraction of the AA smooth muscle cell, and the mechanics of a thick-walled cylinder. The model represents a myogenic response based on a pressure-induced shift in the voltage dependence of calcium channel openings: with increasing transmural pressure, model vessel diameter decreases; and with decreasing pressure, vessel diameter increases. Furthermore, the model myogenic mechanism includes a rate-sensitive component that yields constriction and dilation kinetics similar to behaviors observed in vitro. A parameter set is identified based on physical dimensions of an AA in a rat kidney. Model results suggest that the interaction of Ca2+ and K+ fluxes mediated by voltage-gated and voltage-calcium-gated channels, respectively, gives rise to periodicity in the transport of the two ions. This results in a time-periodic cytoplasmic calcium concentration, myosin light chain phosphorylation, and cross-bridge formation with the attending muscle stress. Furthermore, the model predicts myogenic responses that agree with experimental observations, most notably those which demonstrate that the renal AA constricts in response to increases in both steady and systolic blood pressures. The myogenic model captures these essential functions of the renal AA, and it may prove useful as a fundamental component in a multiscale model of the renal microvasculature suitable for investigations of the pathogenesis of hypertensive renal diseases.

scholarly journals Evaluation of 2D super-resolution ultrasound imaging of the rat renal vasculature using ex vivo micro-computed tomography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sofie Bech Andersen ◽  
Iman Taghavi ◽  
Hans Martin Kjer ◽  
Stinne Byrholdt Søgaard ◽  
Carsten Gundlach ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Rat Kidney ◽  
Vascular Anatomy ◽  
Super Resolution ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Renal Vasculature

AbstractSuper-resolution ultrasound imaging (SRUS) enables in vivo microvascular imaging of deeper-lying tissues and organs, such as the kidneys or liver. The technique allows new insights into microvascular anatomy and physiology and the development of disease-related microvascular abnormalities. However, the microvascular anatomy is intricate and challenging to depict with the currently available imaging techniques, and validation of the microvascular structures of deeper-lying organs obtained with SRUS remains difficult. Our study aimed to directly compare the vascular anatomy in two in vivo 2D SRUS images of a Sprague–Dawley rat kidney with ex vivo μCT of the same kidney. Co-registering the SRUS images to the μCT volume revealed visually very similar vascular features of vessels ranging from ~ 100 to 1300 μm in diameter and illustrated a high level of vessel branching complexity captured in the 2D SRUS images. Additionally, it was shown that it is difficult to use μCT data of a whole rat kidney specimen to validate the super-resolution capability of our ultrasound scans, i.e., validating the actual microvasculature of the rat kidney. Lastly, by comparing the two imaging modalities, fundamental challenges for 2D SRUS were demonstrated, including the complexity of projecting a 3D vessel network into 2D. These challenges should be considered when interpreting clinical or preclinical SRUS data in future studies.

scholarly journals Rapid Action of Aldosterone on Protein Levels of Sodium-Hydrogen Exchangers and Protein Kinase C Beta Isoforms in Rat Kidney

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Somchit Eiam-Ong ◽  
Mookda Chaipipat ◽  
Krissanapong Manotham ◽  
Somchai Eiam-Ong
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Rat Kidney ◽  
Protein Abundance ◽  
Renal Vasculature ◽  
Protein Levels ◽  
Kinase C ◽  
Sodium Hydrogen

Previous in vitro studies demonstrated that aldosterone rapidly activates sodium-hydrogen exchangers 1 and 3 (NHE 1 and 3). In vitro investigations revealed that protein kinase C (PKC) regulates NHE properties. We previously demonstrated that aldosterone rapidly enhances PKCα protein abundance in the rat kidney. There are no reports of renal PKCβ (I and II) protein levels related to the regulation by aldosterone. There are also no in vivo data regarding the rapid effects of aldosterone on renal protein levels of NHE (1 and 3) and PKCβ (I and II), simultaneously. In the current study, rats received normal saline solution or aldosterone (150 μg/kg BW, i.p.). After 30 minutes, abundance and immunoreactivity of these proteins were determined by Western blot analysis and immunohistochemistry, respectively. Aldosterone increased NHE1 and NHE3 protein abundance to 152% and 134%, respectively (P<0.05). PKCβI protein level was enhanced by 30%, whereas PKCβII declined slightly. Aldosterone increased NHE protein expression mostly in the medulla. PKCβI immunostaining intensity was increased in the glomeruli, renal vasculature, and thin limb of the loop of Henle, while PKCβII was reduced. This is the first in vivo study to simultaneously demonstrate that aldosterone rapidly elevates PKCβI and NHE (1 and 3) protein abundance in the rat kidney. Aldosterone-induced NHE (1 and 3) protein levels may be related to PKCβI activation.

The Fine Structure of Rat Renal Microbodies and Cytoplasmic Bodies Following Perfusion Fixation

1973 ◽  
Vol 31 ◽  
pp. 620-621
Author(s):  
J. M. Barrett ◽  
P. M. Heidger
Keyword(s):  
Fine Structure ◽  
Proximal Tubule ◽  
Rat Kidney ◽  
Renal Proximal Tubule ◽  
Convincing Evidence ◽  
Cytoplasmic Bodies ◽  
Rat Renal Proximal Tubule ◽  
Renal Proximal Tubule Cells ◽  
Perfusion Fixation

Microbodies have received extensive morphological and cytochemical investigation since they were first described by Rhodin in 1954. To our knowledge, however, all investigations of microbodies and cytoplasmic bodies of rat renal proximal tubule cells have employed immersion fixation. Tisher, et al. have shown convincing evidence of fine structural alteration of microbodies in rhesus monkey kidney following immersion fixation; these alterations were not encountered when in vivo intravascular perfusion was employed. In view of these studies, and the fact that techniques for perfusion fixation have been established specifically for the rat kidney by Maunsbach, it seemed desirable to employ perfusion fixation to study the fine structure and distribution of microbodies and cytoplasmic bodies within the rat renal proximal tubule.

Pressure Changes Induced by Whole Body Acceleration Shocks

1991 ◽  
Vol 113 (1) ◽  
pp. 27-29 ◽  
Author(s):  
E. Belardinelli ◽  
M. Ursino ◽  
G. Fabbri ◽  
A. Cevese ◽  
F. Schena
Keyword(s):  
Mathematical Model ◽  
Carotid Artery ◽  
Normal Pressure ◽  
Compressed Air ◽  
Whole Body ◽  
Body Acceleration ◽  
Vascular Bed ◽  
Pressure Changes ◽  
The Mathematical Model

In the present paper pressure changes induced by sudden body acceleration are studied “in vivo” on the dog and compared to the results obtainable with a recently developed mathematical model. A dog was fixed to a movable table, which was accelerated by a compressed air piston for less than 1 s. Acceleration was varied by changing the air pressure in the piston. Pressure was measured during the experiment at different points along the vascular bed. However, only data obtained in the carotid artery and abdominal aorta are presented here. The results demonstrated that impulse body accelerations cause significant pressure peaks in the vessel examined (about + 25 mmHg in the carotid artery with body acceleration of g/2). Moreover, pressure changes are rapidly damped, with a time constant of about 0.1s. From the present results it may be concluded that, according to the prediction of the mathematical model, body accelerations such as those occurring in normal life can induce pressure changes well beyond the normal pressure value.

Interactions between ADH and prostaglandins in isolated erythrocyte-perfused rat kidney

1987 ◽  
Vol 252 (2) ◽  
pp. F331-F337 ◽  
Author(s):  
W. Lieberthal ◽  
M. L. Vasilevsky ◽  
C. R. Valeri ◽  
N. G. Levinsky
Keyword(s):  
Sodium Excretion ◽  
Rat Kidney ◽  
Urine Osmolality ◽  
Sodium Reabsorption ◽  
Urinary Osmolality ◽  
Hemodynamic Characteristics ◽  
Urinary Concentrating Ability ◽  
Tubular Morphology ◽  
Isolated Kidneys

Interactions between antidiuretic hormone (ADH) and renal prostaglandins in the regulation of sodium reabsorption and urinary concentrating ability were studied in isolated erythrocyte-perfused rat kidneys (IEPK). In this model, hemodynamic characteristics are comparable to those found in vivo, and tubular morphology is preserved throughout the period of perfusion. [Deamino]-D-arginine vasopressin (dDAVP) markedly reduced fractional sodium excretion (FE Na) in the IEPK from 3.5 +/- 0.6 to 0.45 +/- 0.14%. After indomethacin, FE Na fell still further to 0.08 +/- 0.02%. In the absence of dDAVP indomethacin had no effect on sodium excretion; FE Na was 2.4 +/- 0.6% in control and 2.0 +/- 0.4% in indomethacin-treated groups. dDAVP increased urine osmolality in the IEPK to 741 +/- 26 mosmol/kg. When prostaglandin synthesis was blocked with indomethacin, urinary osmolality increased further to 1,180 +/- 94 mosmol/kg. In isolated kidneys perfused without erythrocytes (IPK), dDAVP decreased FENa from 14.5 +/- 1.8% to 9.6 +/- 1.2%; addition of indomethacin had no further effect. dDAVP increased urine osmolality only modestly to 350 +/- 12 mosmol/kg in the IPK and indomethacin did not increase concentrating ability further (342 +/- 7 mosmol/kg). Thus the IEPK (unlike the IPK) can excrete a markedly hypertonic urine in response to ADH. ADH also enhances tubular reabsorption of sodium in the IEPK. Prostaglandins inhibit both these actions of ADH but do not directly affect sodium excretion in the absence of the hormone.

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