scholarly journals Frequency modulation of renal myogenic autoregulation by perfusion pressure

2007 ◽  
Vol 293 (3) ◽  
pp. R1199-R1204 ◽  
Author(s):  
Xuemei Wang ◽  
Rodger D. Loutzenhiser ◽  
William A. Cupples
Keyword(s):  
Perfusion Pressure ◽  
Function Analysis ◽  
Renal Perfusion ◽  
Tubuloglomerular Feedback ◽  
Operating Frequency ◽  
Systemic Injection ◽  
Transfer Function Analysis ◽  
Blood Flow Dynamics

Recent studies of renal autoregulation have shown modulation of the faster myogenic mechanism by the slower tubuloglomerular feedback and that the modulation can be detected in the dynamics of the myogenic mechanism. Conceptual and empirical considerations suggest that perfusion pressure may modulate the myogenic mechanism, although this has not been tested to date. Here we present data showing that the myogenic operating frequency, assessed by transfer-function analysis, varied directly as a function of perfusion pressure in the hydronephrotic kidney perfused in vitro over the range from 80 to 140 mmHg. A similar result was obtained in intact kidneys in vivo when renal perfusion pressure was altered by systemic injection of NG-nitro-l-arginine methyl ester (l-NAME). When perfusion pressure was not allowed to increase, l-NAME did not affect the myogenic operating frequency despite equivalent reduction of renal vascular conductance. Blood-flow dynamics were assessed in the superior mesenteric artery before and after l-NAME. In this vascular bed, the operating frequency of the myogenic mechanism was not affected by perfusion pressure. Thus the operating frequency of the renal myogenic mechanism is modulated by perfusion pressure independently of tubuloglomerular feedback, and the data suggest some degree of renal specificity of this response.

Dynamic autoregulation in the in vitro perfused hydronephrotic rat kidney

1998 ◽  
Vol 275 (1) ◽  
pp. F126-F130 ◽  
Author(s):  
William A. Cupples ◽  
Rodger D. Loutzenhiser
Keyword(s):  
Function Analysis ◽  
Rat Kidney ◽  
Pressure Fluctuations ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Passive Behavior ◽  
Perfusate Flow ◽  
Transfer Function Analysis

Renal autoregulation is mediated by tubuloglomerular feedback, operating at 0.03–0.05 Hz, and a faster system, operating at 0.1–0.2 Hz, that has been attributed by exclusion to myogenic vasoconstriction. In this study, we examined dynamic autoregulation in the hydronephrotic rat kidney, which lacks tubuloglomerular feedback but exhibits pressure-induced afferent arteriolar vasoconstriction. Kidneys were harvested under anesthesia from Sprague-Dawley rats and perfused in vitro using defined, colloid-free medium. Renal perfusate flow was assessed during forced pressure fluctuations at mean pressures of 60–140 mmHg. Transfer function analysis revealed passive behavior at 60 mmHg and active, pressure-dependent responses at higher pressures. In all cases, coherence was high (0.89 ± 0.03 between 0.01 and 0.9 Hz). There was a resonance peak in admittance gain at ≈0.3 Hz and an associated broad peak in phase angle. Below this frequency, gain declined progressively. The minimum gain achieved at 0.01–0.05 Hz was pressure sensitive, being 1.08 ± 0.02 at 60 mmHg and 0.71 ± 0.04 at 140 mmHg. These findings are consistent with in vivo results and with model-based predictions of the dynamics of myogenic autoregulation, supporting the postulate that the rapid component of autoregulation reflects operation of a myogenic mechanism.

scholarly journals High-salt diet blunts renal autoregulation by a reactive oxygen species-dependent mechanism

2014 ◽  
Vol 307 (1) ◽  
pp. F33-F40 ◽  
Author(s):  
Robert C. Fellner ◽  
Anthony K. Cook ◽  
Paul M. O'Connor ◽  
Shali Zhang ◽  
David M. Pollock ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
High Salt ◽  
Ros Generation ◽  
Dietary Salt ◽  
Salt Diet ◽  
Renal Perfusion Pressure

High dietary salt is common in Western countries and is an important contributor to increased cardiovascular disease. Autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) is an essential function of the renal microcirculation that could be affected by excessive dietary salt. High salt (HS) increases renal ROS generation partly by the enzyme NADPH oxidase. We hypothesized that a HS diet would impair autoregulation via NADPH oxidase-dependent ROS generation. The role of NADPH-dependent ROS production on the blunted autoregulatory response with a HS diet was assessed in vitro and in vivo using the blood-perfused juxtamedullary nephron preparation and anesthetized rats, respectively. The increase in renal lipid peroxidation and p67 phox expression induced by HS was prevented by apocynin treatment. Control afferent arterioles exhibited normal autoregulatory behavior in response to acute increases in renal perfusion pressure, whereas arterioles from HS rats exhibited a blunted response. Autoregulatory behavior in HS rats was restored in vitro by acute exposure to the NADPH oxidase inhibitor apocynin. At the whole kidney level, in vivo experiments showed that both RBF and GFR declined in HS rats when left kidney renal perfusion pressure was reduced from ambient to 95 mmHg, whereas control rats maintained stable GFR and RBF consistent with efficient autoregulatory behavior. Apocynin treatment improved in vivo autoregulatory behavior in HS rats and had no detectable effect in normal salt diet-fed rats. These data support the hypothesis that impaired renal autoregulatory behavior in rats fed a HS diet is mediated by NADPH oxidase-derived ROS.

P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function

2002 ◽  
Vol 82 (1) ◽  
pp. 131-185 ◽  
Author(s):  
Richard J. Roman
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Vascular Tone ◽  
Mesangial Cells ◽  
Cardiovascular Function ◽  
Tubuloglomerular Feedback ◽  
Peripheral Vasculature ◽  
Therapeutic Benefits

Recent studies have indicated that arachidonic acid is primarily metabolized by cytochrome P-450 (CYP) enzymes in the brain, lung, kidney, and peripheral vasculature to 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) and that these compounds play critical roles in the regulation of renal, pulmonary, and cardiac function and vascular tone. EETs are endothelium-derived vasodilators that hyperpolarize vascular smooth muscle (VSM) cells by activating K+channels. 20-HETE is a vasoconstrictor produced in VSM cells that reduces the open-state probability of Ca2+-activated K+channels. Inhibitors of the formation of 20-HETE block the myogenic response of renal, cerebral, and skeletal muscle arterioles in vitro and autoregulation of renal and cerebral blood flow in vivo. They also block tubuloglomerular feedback responses in vivo and the vasoconstrictor response to elevations in tissue Po2both in vivo and in vitro. The formation of 20-HETE in VSM is stimulated by angiotensin II and endothelin and is inhibited by nitric oxide (NO) and carbon monoxide (CO). Blockade of the formation of 20-HETE attenuates the vascular responses to angiotensin II, endothelin, norepinephrine, NO, and CO. In the kidney, EETs and 20-HETE are produced in the proximal tubule and the thick ascending loop of Henle. They regulate Na+transport in these nephron segments. 20-HETE also contributes to the mitogenic effects of a variety of growth factors in VSM, renal epithelial, and mesangial cells. The production of EETs and 20-HETE is altered in experimental and genetic models of hypertension, diabetes, uremia, toxemia of pregnancy, and hepatorenal syndrome. Given the importance of this pathway in the control of cardiovascular function, it is likely that CYP metabolites of arachidonic acid contribute to the changes in renal function and vascular tone associated with some of these conditions and that drugs that modify the formation and/or actions of EETs and 20-HETE may have therapeutic benefits.

Membrane potential measurements in renal afferent and efferent arterioles: actions of angiotensin II

1997 ◽  
Vol 273 (2) ◽  
pp. F307-F314 ◽  
Author(s):  
R. Loutzenhiser ◽  
L. Chilton ◽  
G. Trottier
Keyword(s):  
Angiotensin Ii ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Renal Perfusion ◽  
Membrane Potentials ◽  
Ang Ii ◽  
Ca Channels ◽  
Renal Perfusion Pressure

An adaptation of the in vitro perfused hydronephrotic rat kidney model allowing in situ measurement of arteriolar membrane potentials is described. At a renal perfusion pressure of 80 mmHg, resting membrane potentials of interlobular arteries (22 +/- 2 microns) and afferent (14 +/- 1 microns) and efferent arterioles (12 +/- 1 microns) were -40 +/- 2 (n = 8), -40 +/- 1 (n = 45), and -38 +/- 2 mV (n = 22), respectively (P = 0.75). Using a dual-pipette system to stabilize the impalement site, we measured afferent and efferent arteriolar membrane potentials during angiotensin II (ANG II)-induced vasoconstriction. ANG II (0.1 nM) reduced afferent arteriolar diameters from 13 +/- 1 to 8 +/- 1 microns (n = 8, P = 0.005) and membrane potentials from -40 +/- 2 to -29 +/- mV (P = 0.012). ANG II elicited a similar vasoconstriction in efferent arterioles, decreasing diameters from 13 +/- 1 to 8 +/- 1 microns (n = 8, P = 0.004), but failed to elicit a significant depolarization (-39 +/- 2 for control; -36 +/- 3 mV for ANG II; P = 0.27). Our findings thus indicate that resting membrane potentials of pre- and postglomerular arterioles are similar and lie near the threshold activation potential for L-type Ca channels. ANG II-induced vasoconstriction appears to be closely coupled to membrane depolarization in the afferent arteriole, whereas mechanical and electrical responses appear to be dissociated in the efferent arteriole.

Structure–function analysis of full-length midkine reveals novel residues important for heparin binding and zebrafish embryogenesis

2013 ◽  
Vol 451 (3) ◽  
pp. 407-415 ◽  
Author(s):  
Jackwee Lim ◽  
Sheng Yao ◽  
Martin Graf ◽  
Christoph Winkler ◽  
Daiwen Yang
Keyword(s):  
Function Analysis ◽  
Structural Features ◽  
Full Length ◽  
Domain Growth ◽  
Heparin Binding ◽  
Cellular Mechanisms ◽  
The Individual ◽  
Zebrafish Embryogenesis

Midkine is a heparin-binding di-domain growth factor, implicated in many biological processes as diverse as angiogenesis, neurogenesis and tumorigenesis. Elevated midkine levels reflect poor prognosis for many carcinomas, yet the molecular and cellular mechanisms orchestrating its activity remain unclear. At the present time, the individual structures of isolated half domains of human midkine are known and its functionally active C-terminal half domain remains a popular therapeutic target. In the present study, we determined the structure of full-length zebrafish midkine and show that it interacts with fondaparinux (a synthetic highly sulfated pentasaccharide) and natural heparin through a previously uncharacterized, but highly conserved, hinge region. Mutating six consecutive residues in the conserved hinge to glycine strongly abates heparin binding and midkine embryogenic activity. In contrast with previous in vitro studies, we found that the isolated C-terminal half domain is not active in vivo in embryos. Instead, we have demonstrated that the N-terminal half domain is needed to enhance heparin binding and mediate midkine embryogenic activity surprisingly in both heparin-dependent and -independent manners. Our findings provide new insights into the structural features of full-length midkine relevant for embryogenesis, and unravel additional therapeutic routes targeting the N-terminal half domain and conserved hinge.

Effects of ATP on pre- and postglomerular juxtamedullary microvasculature

1992 ◽  
Vol 263 (5) ◽  
pp. F886-F893 ◽  
Author(s):  
E. W. Inscho ◽  
K. Ohishi ◽  
L. G. Navar
Keyword(s):  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Renal Perfusion Pressure ◽  
Organ Systems ◽  
Smooth Muscle Function ◽  
Juxtamedullary Nephron ◽  
Afferent Arterioles ◽  
The Right ◽  
Dose Dependent

Based on evidence that extracellular ATP can influence vascular smooth muscle function in other organ systems, experiments were conducted to characterize the responsiveness of rat juxtamedullary microvascular segments to ATP. Experiments were performed using the in vitro blood-perfused juxtamedullary nephron preparation combined with video microscopy. Pentobarbital-anesthetized rats were pretreated with enalaprilat (2 mg iv) for 30 min before the right kidney was isolated and prepared for study. Renal perfusion pressure was set at 110 mmHg and held constant. Under control conditions, afferent and efferent arteriolar diameters averaged 19.9 +/- 1.4 (n = 19) and 21.6 +/- 1.2 microns (n = 10), respectively. Superfusion with 1, 10, and 100 microM ATP solutions induced sustained dose-dependent afferent vasoconstriction of 8.3 +/- 1.4, 12.8 +/- 1.7, and 12.1 +/- 2.1%, respectively (P < 0.01). Afferent vasoconstrictor responses to ATP were also observed during adenosine receptor blockade. In contrast, efferent arterioles were unresponsive to ATP stimulation even at concentrations as high as 100 microM (P > 0.05). Arcuate and interlobular arterial diameters averaged 82.0 +/- 15.7 (n = 5) and 43.4 +/- 4.5 microns (n = 6), respectively, during control conditions and responded to ATP treatment with a transient vasoconstriction followed by a gradual return to control diameter. Interlobular arteries exhibited a sustained constriction only at the 100 microM concentration (P < 0.05). These data demonstrate that afferent arterioles are more responsive to ATP treatment than other renal microvascular segments and suggest the presence of ATP-sensitive P2x purinoceptors on pre- but not postglomerular juxtamedullary microvascular elements.

scholarly journals An Experimental Approach to Evaluate the Dynamic Behavior of the Human Knee

1988 ◽  
Vol 110 (1) ◽  
pp. 69-73 ◽  
Author(s):  
H. W. J. Jans ◽  
L. J. M. G. Dortmans ◽  
A. A. H. J. Sauren ◽  
A. Huson
Keyword(s):  
Experimental Approach ◽  
Function Analysis ◽  
Measuring System ◽  
Dynamic Force ◽  
Force Transmission ◽  
Human Knee ◽  
Human Knee Joint ◽  
In Vitro Investigation ◽  
Transfer Function Analysis

An experimental approach for an in vitro investigation of some aspects of dynamic force transmission through the human knee joint is presented. Essentially, the behavior of the joint was analyzed by measuring the responses to low level random excitation of the tibia while the femur was clamped. A global equilibrium position of the joint was attained by exerting static forces on the tibia via three tendinous muscle attachments. The responses to the applied dynamic loads were measured using a multi-channel dynamic measuring system and quantified by means of transfer function analysis techniques. Some preliminary experimental results are presented to illustrate the effects of variation of the direction and the magnitude of the applied dynamic and static loads.

Neuronal NOS contributes to biphasic autoregulatory response during enhanced TGF activity

1999 ◽  
Vol 277 (1) ◽  
pp. F113-F120 ◽  
Author(s):  
Atsuhiro Ichihara ◽  
L. Gabriel Navar
Keyword(s):  
Initial Response ◽  
Renal Perfusion ◽  
Tubuloglomerular Feedback ◽  
Afferent Arterioles ◽  
Series Of Experiments ◽  
Oxide Synthase ◽  
Increased Activity ◽  
Arteriolar Diameter ◽  
Distal Delivery

To assess the afferent arteriolar autoregulatory response during increased activity of the tubuloglomerular feedback (TGF) mechanism and to delineate the contribution of neuronal nitric oxide synthase (nNOS) to this response, afferent arteriolar diameter responses to changes in renal perfusion pressure (RPP) were monitored in vitro using the blood-perfused rat juxtamedullary nephron preparation. At RPP of 100 mmHg, basal afferent arteriolar diameter averaged 21.1 ± 1.4 μm ( n = 9). The initial and sustained constrictor responses of afferent arterioles to a 60-mmHg increase in RPP averaged 14.8 ± 1.4% and 13.3 ± 1.3%, respectively. Acetazolamide treatment, which enhances TGF responsiveness by increasing distal nephron volume delivery, significantly decreased basal afferent arteriolar diameter by 8.2 ± 0.5% and enhanced the initial response (25.5 ± 2.3%) to a 60-mmHg increase in RPP but did not alter the sustained response (14.3 ± 1.5%). In another series of experiments, nNOS inhibition with 10 μM S-methyl-l-thiocitrulline (l-SMTC) significantly decreased afferent arteriolar diameter from 20.3 ± 1.3 to 18.3 ± 1.1 μm ( n = 7) and enhanced both the initial (34.4 ± 3.5%) and sustained constrictor responses (27.6 ± 2.9%) to a 60-mmHg increase in RPP. Treatment with acetazolamide further enhanced both initial (56.4 ± 3.0%) and sustained responses (54.6 ± 2.7%). Interruption of distal delivery by transection of the loops of Henle prevented the enhanced responses to increases in RPP elicited with either acetazolamide orl-SMTC. These results indicate that nNOS contributes to the counteracting resetting process of biphasic afferent arteriolar constrictor responses to increases in RPP through a TGF-dependent mechanism.

scholarly journals Structure-Function Analysis of Escherichia coli MnmG (GidA), a Highly Conserved tRNA-Modifying Enzyme

2009 ◽  
Vol 191 (24) ◽  
pp. 7614-7619 ◽  
Author(s):  
Rong Shi ◽  
Magda Villarroya ◽  
Rafael Ruiz-Partida ◽  
Yunge Li ◽  
Ariane Proteau ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Conformational Changes ◽  
Function Analysis ◽  
Trna Modification ◽  
Conserved Residues ◽  
Limited Trypsinolysis ◽  
Fad Binding ◽  
Trna Binding

ABSTRACT The MnmE-MnmG complex is involved in tRNA modification. We have determined the crystal structure of Escherichia coli MnmG at 2.4-Å resolution, mutated highly conserved residues with putative roles in flavin adenine dinucleotide (FAD) or tRNA binding and MnmE interaction, and analyzed the effects of these mutations in vivo and in vitro. Limited trypsinolysis of MnmG suggests significant conformational changes upon FAD binding.

scholarly journals In VitroModel for Studying Malignancy Associated Changes

2003 ◽  
Vol 25 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Xiao Rong Sun ◽  
Yonghong Zheng ◽  
Calum MacAulay ◽  
Stephen Lam ◽  
Alexei Doudkine ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Function Analysis ◽  
Cancer Cell Line ◽  
Bronchial Epithelium ◽  
Lung Cancer Cell Line ◽  
Human Respiratory Tract ◽  
Normal Cells ◽  
Nuclear Features

Malignancy associated changes (MAC) can be defined as subtle morphological and physiologic changes that are found in ostensibly normal cells of patients harboring malignant disease. It has been postulated that MAC have a potential to become a useful tool in detection, diagnosis and prognosis of malignant diseases. An in vitro cell culture model system was designed to study interactions between non‐small cell lung cancer (NSCLC) and the normal bronchial epithelium of the human respiratory tractin vivoto see if the MAC‐like phenomenon can be detected in such a system. In this study we examined changes in nuclear features of normal human bronchial epithelial cells (NHBE) when they were co‐cultured with cells derived from a lung cancer cell line NCI‐H460. Using discriminant function analysis, nuclear features were determined which allow maximal discrimination between normal cells incubated with or without cancerous cells. Our results demonstrate that MAC appear to be specific to changes induced by malignancy, and that these changes differ from those induced by growth factors in the serum. This study provides evidence in support to the hypothesis that MAC are induced by a soluble factor(s) released by malignant cells. Colour figure can be viewed onhttp://www.esacp.org/acp/2003/25‐2/sun.htm.

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