BACKGROUND: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space. OBJECTIVE: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats. METHODS: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blue + hyaluronidase, or (3) Evans blue + hyaluronidase + 20% human albumin via the tail vein. Spectrophotometric analysis was performed 2 h later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle. RESULTS: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (P < 0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (P < 0.011). CONCLUSION: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.

• MeSH
• albuminy * metabolismus   MeSH
• cévní endotel účinky léků   metabolismus   MeSH
• Evansova modř MeSH
• glykokalyx * metabolismus   účinky léků   MeSH
• hyaluronoglukosaminidasa farmakologie   MeSH
• kapilární permeabilita * účinky léků   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

It was suggested that impaired β-adrenergic relaxation in spontaneously hypertensive rats (SHR) might contribute to their high blood pressure (BP). Our study was focused on isoprenaline-induced dilatation of conduit femoral or resistance mesenteric arteries and on isoprenaline-induced BP reduction in SHR and Wistar-Kyoto rats (WKY). We confirmed decreased β-adrenergic relaxation of SHR femoral arteries due to the absence of its endothelium-independent component, whereas endothelium-dependent component of β-adrenergic smooth muscle relaxation was similar in both strains. Conversely, isoprenaline-induced relaxation of resistance mesenteric arteries was similar in both strains and this was true for endothelium-dependent and endothelium-independent components. We observed moderately reduced sensitivity of SHR mesenteric arteries to salmeterol (β2-adrenergic agonist) and this strain difference disappeared after endothelium removal. However, there was no difference in mesenteric arteries relaxation by dobutamine (β1-adrenergic agonist) which was independent of endothelium. The increasing isoprenaline doses elicited similar BP decrease in both rat strains, although BP sensitivity to isoprenaline was slightly decreased in SHR. The blockade of cyclooxygenase (indomethacin) and NO synthase (L-NAME) further reduced BP sensitivity to isoprenaline in SHR. On the other hand, salmeterol elicited similar BP decrease in both strains and the blockade of cyclooxygenase and NO synthase increased BP sensitivity to salmeterol in SHR as compared to WKY. In conclusion, attenuated β-adrenergic vasodilatation of conduit arteries of SHR but similar β-adrenergic relaxation of resistance mesenteric arteries from WKY and SHR and their similar BP response to β-adrenergic agonists do not support major role of altered β-adrenergic vasodilatation for high BP in genetic hypertension.

• MeSH
• adrenergní látky * MeSH
• agonisté adrenergních beta-receptorů farmakologie   MeSH
• arteriae mesentericae MeSH
• cévní endotel MeSH
• cévní rezistence MeSH
• cyklooxygenasy MeSH
• hypertenze * MeSH
• isoprenalin farmakologie   MeSH
• krysa rodu rattus MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• salmeterol xinafoát MeSH
• synthasa oxidu dusnatého MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• cévní endotel * fyziologie   patofyziologie   MeSH
• glykokalyx * fyziologie   ultrastruktura   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Cíl: Analyzovat souvislost mezi podáním reversinu a zvýšenou plasticitou buněk DFAT schopných dělení na různé typy buněk. Metoda: Vykultivované buňky DFAT byly rozděleny do čtyř skupin podle dávky reversinu: na kontrolní (bez reversinu) skupinu a na skupiny s aplikací reversinu v dávkách 10 nM, 20 nM a 40 nM. Každá skupina prochází několika stadii vývoje před další diferenciací na kardiomyocyty (identifikované expresí cTnT), buňky hladké svaloviny (vascular smooth muscle cells, VSMC) (označené expresí afta-SMA) a buňky cévního endotelu (identifikované expresí CD31). Výsledek: V každé skupině buněk DFAT s aplikací reversinu byly nalezeny statisticky významné rozdíly v expresi cTnT, alfa-SMA a CD31 (p = 0,003; resp. < 0,001 a < 0,001). Post hoc analýza s použitím Tukeyova testu prokázala, že pouze ve skupině s reversinem v dávce 10 nM došlo ke statisticky významnému rozdílu oproti kontrolní skupině (p = 0,002) v expresi cTnT a ve skupinách s reversinem v dávkách 10 nM a 20 nM k rozdílu v expresi alfa-SMA a CD31 (p = 0,028, resp. p < 0,001). Závěry: Tato studie prokázala vztah mezi dávkou reversinu a zvýšenou plasticitou buněk DFAT schopných diferenciace na kardiomyocyty (cTnT), VSMC (alfa-SMA) a buňky cévního endotelu (CD31).

Aim: To analyze the association between reversine and increased plasticity of DFAT into cardiac derivative cells. Method: The cultured DFAT cells were divided into four groups based on reversine dose: control (no reversine), 10 nM, 20 nM, and 40 nM reversine. Each group will go through several stages of passage before further differentiation into cardiomyocytes (marked by cTnT expression), VSCMs (marked by alpha-SMA expression), and vascular endothelial cells (marked by alpha-SMA expression) (marked by CD31 expression). Result: There were significant differences in the expression of cTnT, alpha-SMA, and CD31 (p = 0.003, p <0.001, and p <0.001, respectively) in each group of DFAT cells that received reversine. From post-hoc analysis with Tukey test, it was found that only the 10 nM reversine group produced a significant difference compared to the control group (p = 0.002) for cTnT expression and reversine 10 nM and 20 nM group for α-SMA expression and CD31 expression (p = 0.028 and p <0.001, respectively). Conclusions: This study proves that there is a relationship between reversine and increased plasticity of DFAT cells into cardiac derived cells in the form of cardiomyocytes (cTnT), VSMCs (alpha-SMA), and vascular endothelial cells (CD31).

• Klíčová slova
• reversine,
• MeSH
• cévní endotel * účinky léků   MeSH
• endoteliální buňky účinky léků   MeSH
• inhibitory proteinkinas farmakologie   terapeutické užití   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• plasticita buňky * účinky léků   MeSH
• Check Tag
• lidé MeSH

• MeSH
• cévní endotel účinky léků   MeSH
• diabetes mellitus farmakoterapie   MeSH
• diabetické nefropatie prevence a kontrola   MeSH
• glukagonu podobný peptid 1 * farmakologie   terapeutické užití   MeSH
• hmotnostní úbytek účinky léků   MeSH
• inhibitory dipeptidylpeptidasy 4 * farmakologie   terapeutické užití   MeSH
• krevní tlak účinky léků   MeSH
• ledviny * účinky léků   MeSH
• lidé MeSH
• natriuréza účinky léků   MeSH
• oxidační stres účinky léků   MeSH
• Check Tag
• lidé MeSH

The kinin receptors are classically involved in inflammation, pain and sepsis. The effects of the kinin B1 receptor agonist des-Arg9-bradykinin (DBK) and lipopolysaccharide (LPS) were investigated by comparing the membrane potential responses of aortic rings from transgenic rats overexpressing the kinin B1 receptor (B1R) in the endothelium (TGR(Tie2B1)) and Sprague Dawley (SD) rats. No difference in the resting membrane potential in the aorta's smooth muscle from the transgenic and SD rats was observed. The aorta rings from SD rats hyperpolarized only to LPS but not to DBK, whereas the aorta rings from TGR(Tie2B1) responded by the administration of both drugs. DBK and LPS responses were inhibited by the B1 receptor antagonist R715 and by iberiotoxin in both cases. Thapsigargin induced a hyperpolarization in the smooth muscle of SD rats that was not reversed by R715, but was reversed by iberiotoxin and this hyperpolarization was further augmented by DBK administration. These results show that the model of overexpression of vascular B1 receptors in the TGR(Tie2B1) rats represent a good model to study the role of functional B1 receptors in the absence of any pathological stimulus. The data also show that KCa channels are the final mediators of the hyperpolarizing responses to DBK and LPS. In addition, we suggest an interaction between the B1R and TLR4, since the hyperpolarization induced by LPS could be abolished in the presence of R715.

• MeSH
• aorta MeSH
• bradykinin * farmakologie   MeSH
• cévní endotel MeSH
• krysa rodu rattus MeSH
• lipopolysacharidy farmakologie   MeSH
• membránové potenciály MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• receptor bradykininu B1 * genetika   MeSH
• techniky in vitro MeSH
• thapsigargin farmakologie   MeSH
• toll-like receptor 4 MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

x

x

• MeSH
• cévní endotel patologie   MeSH
• fibrin-fibrinogen - produkty degradace analýza   MeSH
• heparin nízkomolekulární aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• heparin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• INR metody   MeSH
• komplikace těhotenství * etiologie   MeSH
• lidé MeSH
• natriuretický peptid typu B MeSH
• rentgendiagnostika MeSH
• rezistence k aktivovanému proteinu C komplikace   patologie   MeSH
• rizikové faktory MeSH
• trombektomie metody   MeSH
• warfarin farmakologie   škodlivé účinky   toxicita   MeSH
• žilní tromboembolie farmakoterapie   patofyziologie   MeSH
• žilní trombóza * farmakoterapie   patofyziologie   MeSH
• Check Tag
• lidé MeSH

• MeSH
• biologické markery MeSH
• buněčná adheze MeSH
• cévní buněčněadhezivní molekula-1 metabolismus   MeSH
• cévní endotel metabolismus   MeSH
• karcinom z přechodných buněk * MeSH
• lidé MeSH
• mezibuněčná adhezivní molekula-1 metabolismus   MeSH
• močový měchýř MeSH
• nádory močového měchýře * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH

Exercise training (ET) is well established to induce vascular adaptations on the metabolically active muscles. These adaptations include increased function of vascular potassium channels and enhanced endothelium-dependent relaxations. However, the available data on the effect of ET on vasculatures that normally constrict during exercise, such as mesenteric arteries (MA), are scarce and not conclusive. Therefore, this study hypothesized that 10 weeks of moderate-intensity ET would result in adaptations towards more vasoconstriction or/and less vasodilatation of MA. Young Fischer 344 rats were randomly assigned to a sedentary group (SED; n=24) or exercise training group (EXE; n=28). The EXE rats underwent a progressive treadmill ET program for 10 weeks. Isometric tensions of small (SED; 252.9+/-29.5 microm, EXE; 248.6+/-34.4 microm) and large (SED; 397.7+/-85.3 microm, EXE; 414.0+/-86.95 microm) MA were recorded in response to cumulative phenylephrine concentrations (PE; 0-30 microM) in the presence and absence of the BKCa channel blocker, Iberiotoxin (100 nM). In another set of experiments, tensions in response to cumulative concentration-response curves of acetylcholine (ACh) or sodium nitroprusside (SNP) were obtained, and pEC50s were compared. Immunoblotting was performed to measure protein expression levels of the BKCa channel subunits and eNOS. ET did not alter the basal tension of small and large MA but significantly increased their responses to PE, and reduced the effect of BKCa channels in opposing the contractile responses to PE without changes in the protein expression level of BKCa subunits. ET also elicited a size-dependent functional adaptations that involved reduced endothelium-independent and endothelium-dependent relaxations. In large MA the sensitivity to SNP was decreased more than in small MA suggesting impaired nitric oxide (NO)-dependent mechanisms within the vascular smooth muscle cells of ET group. Whereas the shift in pEC50 of ACh-induced relaxation of small MA would suggest more effect on the production of NO within the endothelium, which is not changed in large MA of ET group. However, the eNOS protein expression level was not significantly changed between the ET and SED groups. In conclusion, our results indicate an increase in contraction and reduced relaxation of MA after 10 weeks of ET, an adaptation that may help shunt blood flow to metabolically active tissues during acute exercise.

• MeSH
• arteriae mesentericae MeSH
• cévní endotel metabolismus   MeSH
• krysa rodu rattus MeSH
• nitroprusid farmakologie   MeSH
• oxid dusnatý * metabolismus   MeSH
• vazodilatace * MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Endothelial cell (EC) glycocalyx (GLX) comprise a multicomponent layer of proteoglycans and glycoproteins. Alteration of its integrity contributes to chronic vascular inflammation and leads to the development of cardiovascular diseases. Myeloperoxidase (MPO), a highly abundant enzyme released by polymorphonuclear neutrophils, binds to the GLX and deleteriously affects vascular EC functions. The focus of this study was to elucidate the mechanisms of MPO-mediated alteration of GLX molecules, and to unravel subsequent changes in endothelial integrity and function. MPO binding to GLX of human ECs and subsequent internalization was mediated by cell surface heparan sulfate chains. Moreover, interaction of MPO, which is carrying a cationic charge, with anionic glycosaminoglycans (GAGs) resulted in reduction of their relative charge. By means of micro-viscometry and atomic force microscopy, we disclosed that MPO can crosslink GAG chains. MPO-dependent modulation of GLX structure was further supported by alteration of wheat germ agglutinin staining. Increased expression of ICAM-1 documented endothelial cell activation by both catalytically active and also inactive MPO. Furthermore, MPO increased vascular permeability connected with reorganization of intracellular junctions, however, this was dependent on MPO's catalytic activity. Novel proteins interacting with MPO during transcytosis were identified by proteomic analysis. Altogether, these findings provide evidence that MPO through interaction with GAGs modulates overall charge of the GLX, causing modification of its structure and thus affecting EC function. Importantly, our results also suggest a number of proteins interacting with MPO that possess a variety of cellular localizations and functions.

• MeSH
• cévní endotel MeSH
• endoteliální buňky MeSH
• lidé MeSH
• neutrofily MeSH
• peroxidasa * MeSH
• proteomika * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH