Bradykinin shifts endothelial fluid passage from para- to transcellular routes

Riethmüller, Christoph; Jungmann, Pia M.; Wegener, Joachim; Oberleithner, Hans

doi:10.1007/s00424-006-0121-2

Cited by 16 publications

(17 citation statements)

References 41 publications

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“…Again, as explained above, BK has been shown to exert opposite effects on many biological systems (Crocker and Willavoys, 1975;Riethmü ller et al, 2006), dependent on the experimental conditions as well as the signaling pathways involved. The discrepancy between our and Gekle's studies could be explained as follows.…”

Section: Discussionmentioning

confidence: 87%

“…With the concentration of BK higher than 500 nM, the stimulation became less significant. BK has been reported to exhibit opposite effects on many biological systems (Crocker and Willavoys, 1975;Riethmü ller et al, 2006), dependent on the experimental conditions as well as the signaling pathways involved. Therefore, we speculate that at high concentration (Ͼ500 nM), BK began to affect multiple processes, which led to the overall diminished stimulation of estrone sulfate uptake.…”

Section: Discussionmentioning

confidence: 99%

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Regulation of Human Organic Anion Transporter 3 by Peptide Hormone Bradykinin

Duan²,

You³

2010

The Journal of Pharmacology and Experimental Therapeutics

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Human organic anion transporter (hOAT) 3 belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. In the current study, we examined the regulation of hOAT3 by peptide hormone bradykinin (BK) in COS-7 cells. BK (Յ500 nM) induced a concentration-and time-dependent stimulation of hOAT3 activity, kinetically revealed as an increased V max . Such an increase in V max resulted from an increased cell surface expression without a change in total cell expression of the transporter. BK-induced stimulation of hOAT3 activity could be prevented by treating hOAT3-expressing cells with staurosporine, a general inhibitor for protein kinase C (PKC). To obtain further information on which PKC isoform mediates BK regulation of hOAT3 activity, cellular distribution of various PKC isoforms was examined in cells treated with BK. We showed that BK treatment resulted in a significant translocation of PKC␦, PKC, and PKC from cytosol to membrane. We further showed that BK treatment enhanced association of hOAT3 with PKC␦, PKC, and PKC and that isoform-specific inhibitor for PKC␦, PKC, and PKC reversed BK effect on hOAT3 activity. We therefore concluded that BK stimulated hOAT3 activity through activation of PKC␦, PKC, and PKC, which then led to the redistribution of hOAT3 from the intracellular compartments to the cell surface and to the up-regulation of hOAT3 activity.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Regulation of Human Organic Anion Transporter 3 by Peptide Hormone Bradykinin

Duan²,

You³

2010

The Journal of Pharmacology and Experimental Therapeutics

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“…32 To dilute unbound fluorophores, the FITC-labeled dextran was dialyzed for 24 hours against PBS. For flux measurements, cells (Ϸ2ϫ10 5 /cm 2 ) were seeded onto filter membrane inserts (ThinCert; Greiner; pore diameter 0.4 m) and cultured with or without 0.5 nmol/L aldosterone.…”

Section: Determination Of Endothelial Fluid Permeabilitymentioning

confidence: 99%

C-Reactive Protein Makes Human Endothelium Stiff and Tight

Kusche-Vihrog¹,

Urbanová²,

Blanque³

et al. 2011

Hypertension

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Abstract-Elevation of C-reactive protein (CRP) in human blood accompanies inflammatory processes, including cardiovascular diseases. There is increasing evidence that the acute-phase reactant CRP is not only a passive marker protein for systemic inflammation but also affects the vascular system. Further, CRP is an independent risk factor for atherosclerosis and the development of hypertension. Another crucial player in atherosclerotic processes is the mineralocorticoid hormone aldosterone. Even in low physiological concentrations, it stimulates the expression and membrane insertion of the epithelial sodium channel, thereby increasing the mechanical stiffness of endothelial cells. This contributes to the progression of endothelial dysfunction. In the present study, the hypothesis was tested that the acute application of CRP (25 mg/L), in presence of aldosterone (0.5 nmol/L; 24 hour incubation), modifies the mechanical stiffness and permeability of the endothelium. We found that endothelial cells stiffen in response to CRP. In parallel, endothelial epithelial sodium channel is inserted into the plasma membrane, while, surprisingly, the endothelial permeability decreases. CRP actions are prevented either by the inhibition of the intracellular aldosterone receptors using spironolactone (5 nmol/L) or by the inactivation of epithelial sodium channel using specific blockers. In contrast, inhibition of the release of the vasodilating gas nitric oxide via blockade of the phosphoinositide 3-kinase/Akt pathway has no effect on the CRP-induced stiffening of endothelial cells. The data indicate that CRP enhances the effects of aldosterone on the mechanical properties of the endothelium. Thus, CRP could counteract any decrease in arterial blood pressure that accompanies severe acute inflammatory processes. (Hypertension. 2011; 57:231-237.)Key Words: aldosterone Ⅲ CRP Ⅲ ENaC Ⅲ AFM Ⅲ immunofluorescence Ⅲ PI3K Ⅲ NO C -Reactive protein (CRP) is considered to be a stable and powerful inflammatory marker of future cardiovascular risk 1 and, as an acute-phase reactant, originally considered to be a mere marker of vascular inflammation. However, CRP may also participate directly in the inflammatory process. 2 During inflammation and sepsis, the production of NO is increased, which leads to vasodilation and thus to a drop in blood pressure. 3,4 Recently, CRP was shown to decrease endothelial NO synthase expression 5 via inhibition of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, 6 which suggests that it also has a role in endothelial (dys)function. In clinical studies, it has been shown that in patients with essential hypertension, there is a positive correlation between CRP levels and pulse wave velocity, which is a functional indicator for arterial stiffness. 7,8 When the paradigm shift occurred that CRP was not merely a "reporting" but also an "acting" protein, another shift in understanding took place, namely that the mineralocorticoid hormone aldosterone not only acts on the kidney but also on the cardiovascular sys...

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“…After 5 days of growth, confluence of the cell layer was ascertained exemplarily in killed samples either by AFM or in the permeability assay. The measurement was performed as described before [30]. In brief, FITC-dextran (100-μM final concentration) was added to the upper compartment without causing a hydrostatic pressure.…”

Section: Measurement Of Fluid Permeabilitymentioning

confidence: 99%

Bradykinin does not induce gap formation between human endothelial cells

Jungmann

Wilhelmi

Oberleithner

et al. 2007

Pflugers Arch - Eur J Physiol

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Generally, a formation of paracellular gaps is considered to be the main pathway for fluid passage across endothelia. A model substance for studies in vitro is the vasodilatory peptide bradykinin, which has important functions in inflammation and vascular fluid balance. The mechanisms by which it increases endothelial permeability are not as yet clearly defined. Paracellular gap formation was approached using atomic force microscopy (AFM) on human umbilical vein endothelial cells grown on permeable filter supports. To further distinguish between para- vs transcellular fluid passage, a standard permeability assay was modified by a rapid cooling protocol to specifically inhibit vesicular transport pathways. Cell layers stimulated with bradykinin (1 microM) did not show significant alterations at the cellular junctions. However, gap formation was easily detectable by AFM after addition of the Ca(2+)-ionophore ionomycin (1 microM), which was taken as a positive control for cellular contraction. At 37 degrees C, bradykinin enhanced fluorescein isothiocyanate-dextran permeability by 48 +/- 11%. This was blocked by rapid cooling of the sample, indicating a vesicular mechanism of fluid transport. Contrastingly, ionomycin-induced permeability (259 +/- 43%) persisted after cooling (230 +/- 44%), thereby confirming paracellular gap formation. Accordingly, endocytotic vesicle formation, as detected by fluorescence microscopy, was upregulated by 68 +/- 15% through bradykinin action, while ionomycin did not show a significant effect (7 +/- 26%). The combined results of both permeability and morphometric studies lead to the conclusion that bradykinin promotes transcellular fluid passage rather than increasing paracellular diffusion.

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Bradykinin shifts endothelial fluid passage from para- to transcellular routes

Cited by 16 publications

References 41 publications

Regulation of Human Organic Anion Transporter 3 by Peptide Hormone Bradykinin

Regulation of Human Organic Anion Transporter 3 by Peptide Hormone Bradykinin

C-Reactive Protein Makes Human Endothelium Stiff and Tight

Bradykinin does not induce gap formation between human endothelial cells

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