scholarly journals Attenuation by sphingosine-1-phosphate of rat microvessel acute permeability response to bradykinin is rapidly reversible

2012 ◽  
Vol 302 (10) ◽  
pp. H1929-H1935 ◽  
Author(s):  
R. H. Adamson ◽  
R. K. Sarai ◽  
J. F. Clark ◽  
A. Altangerel ◽  
T. L. Thirkill ◽  
...  
Keyword(s):  
Hydraulic Conductivity ◽  
Partial Inhibition ◽  
Inflammatory Agent ◽  
No Inhibition ◽  
Anesthetized Rats ◽  
Sphingosine 1 Phosphate ◽  
Time Courses ◽  
Mesenteric Microvessels ◽  
Dependent Pathway ◽  
Effector Mechanisms

To evaluate the hypothesis that sphingosine-1-phosphate (S1P) and cAMP attenuate increased permeability of individually perfused mesenteric microvessels through a common Rac1-dependent pathway, we measured the attenuation of the peak hydraulic conductivity ( Lp) in response to the inflammatory agent bradykinin (BK) by either S1P or cAMP. We varied the extent of exposure to each agent (test) and measured the ratio Lptest/ LpBK alone for each vessel (anesthetized rats). S1P (1 μM) added at the same time as BK (concurrent, no pretreatment) was as effective to attenuate the response to BK ( Lp ratio: 0.14 ± 0.05; n = 5) as concurrent plus pretreatment with S1P for 30 min ( Lp ratio: 0.26 ± 0.06; n = 11). The same pretreatment with S1P, but with no concurrent S1P, caused no inhibition of the BK response ( Lp ratio 1.07 ± 0.11; n = 8). The rapid on and off action of S1P demonstrated by these results was in contrast to cAMP-dependent changes induced by rolipram and forskolin (RF), which developed more slowly, lasted longer, and resulted in partial inhibition when given either as pretreatment or concurrent with BK. In cultured endothelium, there was no Rac activation or peripheral cortactin localization at 1 min with RF, but cortactin localization and Rac activation were maximal at 1 min with S1P. When S1P was removed, Rac activation returned to control within 2 min. Because of such differing time courses, S1P and cAMP are unlikely to act through fully common effector mechanisms.

Capillary permeability: atrial peptide action is independent of "protein effect"

1990 ◽  
Vol 259 (5) ◽  
pp. H1351-H1356 ◽  
Author(s):  
V. H. Huxley ◽  
D. J. Meyer
Keyword(s):  
Hydraulic Conductivity ◽  
Bovine Serum Albumin ◽  
Atrial Natriuretic Peptide ◽  
Rana Pipiens ◽  
Capillary Permeability ◽  
Barrier Properties ◽  
Effective Area ◽  
Small Rise ◽  
Mesenteric Microvessels ◽  
Exchange Vessel

Perfusion of exchange microvessels with the vasoactive hormone, atrial natriuretic peptide (AP), acutely and reversibly elevates hydraulic conductivity (Lp) by mechanisms that are, as yet, unknown. This, the first of two studies to characterize AP responses when perfusate composition was altered, specifically focuses on the action of AP when perfusate albumin was lowered to change the transcapillary barrier properties for water by passive mechanisms (protein effect). Perfusion of frog (Rana pipiens) mesenteric microvessels with 1 nM AP in 10 mg/ml bovine serum albumin (BSA) elevated Lp by a median 2.1-fold (range 1.2-2.7, n = 13) from control levels (10 mg/ml BSA). Reduction of perfusate albumin from 10 to 1 mg/ml elicited a small rise in Lp (1.8-fold, n = 10); Lp rose a further 2.1-fold (n = 6) when 1 nM AP was added to 1 mg/ml BSA. Likewise, protein-free perfusion elevated Lp from a median 2.2 to 5.1 X 10(-7) cm.s-1.cmH2O-1 (n = 11); 1 nM AP in protein-free perfusate elevated Lp a further 2.1-fold (n = 8). Thus, regardless of protein content, the response to the peptide was a consistent, twofold increase in exchange vessel Lp (n = 27). These data are consistent with the suggestion that the AP-activated rise in Lp (twofold) occurs via an increase in the effective area of the transcapillary pathway for water without influencing the selectivity properties of the paracellular, albumin-sensitive portion of the barrier.

scholarly journals Cortical Substrate Oxidation during Hyperketonemia in the Fasted Anesthetized Rat in Vivo

2011 ◽  
Vol 31 (12) ◽  
pp. 2313-2323 ◽  
Author(s):  
Lihong Jiang ◽  
Graeme F Mason ◽  
Douglas L Rothman ◽  
Robin A de Graaf ◽  
Kevin L Behar
Keyword(s):  
Time Course ◽  
Ketone Bodies ◽  
Tricarboxylic Acid Cycle ◽  
Metabolic Model ◽  
Substrate Oxidation ◽  
Resonance Spectroscopy ◽  
Neural Function ◽  
Anesthetized Rats ◽  
Time Courses

Ketone bodies are important alternate brain fuels, but their capacity to replace glucose and support neural function is unclear. In this study, the contributions of ketone bodies and glucose to cerebral cortical metabolism were measured in vivo in halothane-anesthetized rats fasted for 36 hours ( n=6) and receiving intravenous [2,4-13C2]-d- β-hydroxybutyrate (BHB). Time courses of 13C-enriched brain amino acids (glutamate-C4, glutamine-C4, and glutamate and glutamine-C3) were measured at 9.4 Tesla using spatially localized 1H-[13C]-nuclear magnetic resonance spectroscopy. Metabolic rates were estimated by fitting a constrained, two-compartment (neuron–astrocyte) metabolic model to the 13C time-course data. We found that ketone body oxidation was substantial, accounting for 40% of total substrate oxidation (glucose plus ketone bodies) by neurons and astrocytes. d- β-Hydroxybutyrate was oxidized to a greater extent in neurons than in astrocytes (∼70:30), and followed a pattern closely similar to the metabolism of [1-13C]glucose reported in previous studies. Total neuronal tricarboxylic acid cycle (TCA) flux in hyperketonemic rats was similar to values reported for normal (nonketotic) anesthetized rats infused with [1-13C]glucose, but neuronal glucose oxidation was 40% to 50% lower, indicating that ketone bodies had compensated for the reduction in glucose use.

Role of endothelial Ca2+ stores in the regulation of hydraulic conductivity of Rana microvessels in vivo

2003 ◽  
Vol 284 (4) ◽  
pp. H1468-H1478 ◽  
Author(s):  
C. A. Glass ◽  
D. O. Bates
Keyword(s):  
Hydraulic Conductivity ◽  
Vascular Permeability ◽  
Store Depletion ◽  
Plasmic Reticulum ◽  
Permeability Increase ◽  
Mesenteric Microvessels ◽  
The Relationship ◽  
Serca Inhibition

Vascular permeability is regulated by endothelial cytosolic Ca2+concentration ([Ca2+]i). To determine whether vascular permeability is dependent on extracellular Ca2+influx or release of Ca2+ from stores, hydraulic conductivity ( L p) was measured in single perfused frog mesenteric microvessels in the presence and absence of Ca2+ influx and store depletion. Prevention of Ca2+ reuptake into stores by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) inhibition increased L p in the absence of extracellular Ca2+ influx. L p was further increased when Ca2+ influx was restored. Depletion of the Ca2+ stores with ionomycin and SERCA inhibition increased L p in the presence and the absence of extracellular Ca2+ influx. However, store depletion in itself did not significantly increase L p in the absence of active Ca2+ release from stores into the cytoplasm. There was a significant positive correlation between baseline permeability and the magnitude of the responses to both Ca2+ store release and Ca2+ influx, indicating that the Ca2+ regulating properties of the endothelial cells may regulate the baseline L p. To investigate the role of Ca2+ stores in regulation of L p, the relationship between SERCA inhibition and store release was studied. The magnitude of the L p increase during SERCA inhibition significantly and inversely correlated with that during store release by Ca2+ ionophore, implying that the degree of store depletion regulates the size of the increase on L p. These data show that microvascular permeability in vivo can be increased by agents that release Ca2+ from stores in the absence of Ca2+ influx. They also show that capacitative Ca2+ entry results in increased L p and that the size of the permeability increase can be regulated by the degree of Ca2+ release.

VEGF and ATP act by different mechanisms to increase microvascular permeability and endothelial [Ca2+]i

2000 ◽  
Vol 279 (4) ◽  
pp. H1625-H1634 ◽  
Author(s):  
T. M. Pocock ◽  
B. Williams ◽  
F. E. Curry ◽  
D. O. Bates
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Hydraulic Conductivity ◽  
Vascular Endothelial ◽  
Store Depletion ◽  
Independent Mechanism ◽  
Intracellular Ca ◽  
Mesenteric Microvessels ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) increases hydraulic conductivity ( L p) by stimulating Ca2+ influx into endothelial cells. To determine whether VEGF-mediated Ca2+ influx is stimulated by release of Ca2+ from intracellular stores, we measured the effect of Ca2+ store depletion on VEGF-mediated increased L p and endothelial intracellular Ca2+ concentration ([Ca2+]i) of frog mesenteric microvessels. Inhibition of Ca2+ influx by perfusion with NiCl2 significantly attenuated VEGF-mediated increased [Ca2+]i. Depletion of Ca2+ stores by perfusion of vessels with thapsigargin did not affect the VEGF-mediated increased [Ca2+]i or the increase in L p. In contrast, ATP-mediated increases in both [Ca2+]i and L p were inhibited by thapsigargin perfusion, demonstrating that ATP stimulated store-mediated Ca2+ influx. VEGF also increased Mn2+ influx after perfusion with thapsigargin, whereas ATP did not. These data showed that VEGF increased [Ca2+]i and L p even when Ca2+ stores were depleted and under conditions that prevented ATP-mediated increases in [Ca2+]iand L p. This suggests that VEGF acts through a Ca2+ store-independent mechanism, whereas ATP acts through Ca2+ store-mediated Ca2+ influx.

scholarly journals Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohamed Helal ◽  
Chuan Yan ◽  
Zhiuyan Gong
Keyword(s):  
Tumor Cells ◽  
Proliferative Response ◽  
Gene Expression Analysis ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Secreted Factors ◽  
Sphingosine 1 Phosphate ◽  
Dependent Pathway ◽  
Stimulation Of

AbstractIt has been well known that tumor progression is dependent on secreted factors not only from tumor cells but also from other surrounding non-tumor cells. In the current study, we investigated the role of cholangiocytes during hepatocarcinogenesis following induction of oncogenic krasV12 expression in hepatocytes using an inducible transgenic zebrafish model. Upon induction of carcinogenesis in hepatocytes, a progressive cell proliferation in cholangiocytes was observed. The proliferative response in cholangiocytes was induced by enhanced lipogenesis and bile acids secretion from hepatocytes through activation of Sphingosine 1 phosphate receptor 2 (S1pr2), a known cholangiocyte receptor involving in cholangiocyte proliferation. Enhancement and inhibition of S1pr2 could accelerate or inhibit cholangiocyte proliferation and hepatocarcinogenesis respectively. Gene expression analysis of hepatocytes and cholangiocytes showed that cholangiocytes stimulated carcinogenesis in hepatocytes via an inflammatory cytokine, Il17a/f1, which activated its receptor (Il17ra1a) on hepatocytes and enhanced hepatocarcinogenesis via an ERK dependent pathway. Thus, the enhancing effect of cholangiocytes on hepatocarcinogenesis is likely via an inflammatory loop.

Sphingosine 1-phosphate prevents platelet-activating factor-induced increase in hydraulic conductivity in rat mesenteric venules: pertussis toxin sensitive

2005 ◽  
Vol 289 (2) ◽  
pp. H840-H844 ◽  
Author(s):  
Fred L. Minnear ◽  
Longkun Zhu ◽  
Pingnian He
Keyword(s):  
Hydraulic Conductivity ◽  
Pertussis Toxin ◽  
Inhibitory Action ◽  
Platelet Activating Factor ◽  
Specific Inhibitor ◽  
Biologically Active ◽  
Endothelial Barrier ◽  
Solute Permeability ◽  
Sphingosine 1 Phosphate

Sphingosine 1-phosphate (S1P) is a biologically active lipid. In vitro, S1P tightens the endothelial barrier, as assessed by a rapid increase in electrical resistance and a decrease in solute permeability. We hypothesized that this activity of S1P would also occur in vivo. Hydraulic conductivity ( Lp), an assessment of endothelial barrier function, was measured in individually perfused venules in rat mesenteries. S1P (1 μM) decreased basal Lp by 63% when basal Lp was between 3.6 and 4.1 × 10−7 cm·s−1·cmH2O−1 but showed no effect when basal Lp was below 2 × 10−7 cm·s−1·cmH2O−1. Under either condition, S1P blocked the sixfold increase in Lp induced by platelet-activating factor (PAF, 10 nM). Perfusion of venules with pertussis toxin (0.1 μg/ml), a specific inhibitor of the inhibitory G protein, Gi, for 3 h did not affect basal Lp or the increased Lp induced by PAF. Pertussis toxin, however, significantly attenuated the inhibitory action of S1P on the PAF-induced increase in Lp, indicating the involvement of the Gi protein. Measurement of endothelial cytoplasmic Ca2+ concentration ([Ca2+]i) in venules loaded with fura-2 AM showed that S1P alone transiently increased basal endothelial [Ca2+]i (from 89 nM to 193 nM) but had no effect on the magnitude and time course of the PAF-induced increase in endothelial [Ca2+]i. These results indicate that S1P functions in vivo to prevent the PAF-induced increase in microvessel permeability. The inhibitory action of S1P involves the pertussis toxin-sensitive Gi protein and is not mediated by prevention of the PAF-induced increase in endothelial [Ca2+]i.

Regulation of capillary hydraulic conductivity in response to an acute change in shear

2005 ◽  
Vol 289 (5) ◽  
pp. H2126-H2135 ◽  
Author(s):  
Min-ho Kim ◽  
Norman R. Harris ◽  
John M. Tarbell
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Hydraulic Conductivity ◽  
Flow Shear ◽  
Fluid Filtration ◽  
Acute Change ◽  
Acute Changes ◽  
Mesenteric Microvessels

The effects of mechanical perturbations (shear stress, pressure) on microvascular permeability primarily have been examined in micropipette-cannulated vessels or in endothelial monolayers in vitro. The objective of this study is to determine whether acute changes in blood flow shear stress might influence measurements of hydraulic conductivity ( Lp) in autoperfused microvessels in vivo. Rat mesenteric microvessels were observed via intravital microscopy. Occlusion of a third-order arteriole with a micropipette was used to divert and increase flow through a nonoccluded capillary or fourth-order arteriolar branch. Transvascular fluid filtration rate in the branching vessel was measured with a Landis technique. Flow (shear)-induced increases in Lp disappeared within 20–30 s of the removal of the shear and could be eliminated with nitric oxide synthase inhibition. The shear-induced increase in Lp was greater in capillaries compared with terminal arterioles. An acute change in shear may regulate Lp by a nitric oxide-dependent mechanism that displays heterogeneity within a microvascular network.

Dynamics of endotoxin fever in the rabbit

1986 ◽  
Vol 60 (5) ◽  
pp. 1504-1510 ◽  
Author(s):  
R. Graener ◽  
J. Werner
Keyword(s):  
Core Temperature ◽  
Dynamic Properties ◽  
Experimental Results ◽  
Evaporative Heat Loss ◽  
Climatic Chamber ◽  
Ambient Temperatures ◽  
Air Temperatures ◽  
Time Courses ◽  
Dynamic Shift ◽  
Effector Mechanisms

To analyze the dynamic properties of body temperature and effector mechanisms during endotoxin fever, both experimental and mathematical procedures were applied. Experiments were carried out on rabbits in a climatic chamber at various ambient temperatures. Salmonella typhosa endotoxin (0.1 microgram/kg) was injected into an ear vein. A biphasic core temperature increase evoked by different effector mechanisms depending on ambient temperature was observed. A mathematical model based on experimental results with nonfebrile rabbits predicts the effector behavior at all ambient temperatures. From a comparison of experimental results with the model prediction, it is concluded that the increase of core temperature during fever is essentially caused by a dynamic shift of the controller characteristics. The effect of the pyrogen may be simulated by a resultant fever-controlling signal that is biphasic but increases more steeply than does core temperature. The analysis suggests that the three possible fever-driving effectors, metabolism, ear blood flow, and respiratory evaporative heat loss, should be controlled by the same resultant signal, although the time courses of the effectors and of core temperature vary distinctly at different air temperatures. The model uses an additive controller structure.

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