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- Bulhak, A, et al.
(författare)
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Protection against myocardial ischaemia/reperfusion injury by PPAR-alpha activation is related to production of nitric oxide and endothelin-1
- 2006
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Ingår i: Basic Research in Cardiology. - : Springer Science and Business Media LLC. - 0300-8428 .- 1435-1803. ; 101:3, s. 244-252
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Tidskriftsartikel (refereegranskat)abstract
- Background Ligands of peroxisome proliferator-activated receptor alpha (PPAR-alpha) have been shown to reduce ischaemia/reperfusion injury. The mechanisms behind this effect are not well known. We hypothesized that activation of PPAR-alpha exerts cardioprotection via a mechanism related to nitric oxide (NO) and endothelin-1 (ET-1). Methods Five groups of anaesthetized open-chest Sprague-Dawley rats were given the PPAR-alpha agonist WY 14643 1 mg/kg (WY; n = 7), dimethyl sulfoxide (DMSO, vehicle for WY; n = 6), the combination of WY and the NO synthase inhibitor N-nitro-L-arginine (L-NNA, 2 mg/kg) (n = 7), L-NNA only (n = 8) or 0.9% sodium chloride (NaCl, vehicle for DMSO and L-NNA; n = 8) i.v. before a 30 min period of coronary artery occlusion followed by 2 h of reperfusion. Infarct size (IS), eNOS and iNOS protein and ET-1 mRNA expression were determined. Results There were no haemodynamic differences between the groups during the experiment. The IS was 78 +/- 3% of the area at risk in the DMSO group and 77 +/- 2% in the NaCl group (P = NS). WY reduced IS to 56 +/- 3% (P < 0.001 vs. DMSO group). When WY was administered in combination with L-NNA the cardioprotective effect was abolished (IS 73 +/- 3%, P < 0.01 vs. WY 14643). L-NNA did not affect IS per se (78 +/- 2%, P = NS). The expression of eNOS but not iNOS protein in ischaemic myocardium from rats was increased in the group given WY (P < 0.05). ET-1 mRNA levels were lower in the ischaemic myocardium following WY administration. Conclusion The results suggest that the PPAR-alpha activation protects the rat myocardium against ischaemia/ reperfusion injury via a mechanism related to production of NO, and possibly ET-1.
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- Cao, YX, et al.
(författare)
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Induces vasodilatation of rat mesenteric artery in vitro mainly by inhibiting receptor-mediated Ca2+-influx and Ca2+-release
- 2005
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Ingår i: Archives of Pharmacal Research. - 1976-3786. ; 28:6, s. 709-715
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the effect of atropine on peripheral vasodilation and the mechanisms involved. The isometric tension of rat mesenteric artery rings was recorded in vitro on a myograph. The results showed that atropine, at concentrations greater than 1 mu M, relaxed the noradrenalin (NA)-precontracted rat mesenteric artery in a concentration-dependent manner. Atropine-induced vasodilatation was mediated, in part, by an endothelium-dependent mechanism, to which endothelium-derived hyperpolarizing factor may contribute. Atropine was able to shift the NA-induced concentration-response curve to the right, in a non-parallel manner, suggesting the mechanism of atropine was not mediated via the alpha(1)-adrenoreceptor. The beta-adrenoreceptor and ATIP sensitive potassium channel, a voltage dependent calcium channel, were not involved in the vasodilatation. However, atropine inhibited the contraction derived from NA and CaCl2 in Ca2+-free medium, in a concentration dependent manner, indicating the vasodilatation was related to the inhibition of extracellular Ca2+ influx through the receptor-operated calcium channels and intracellular Ca2+ release from the Ca (2+) store. Atropine had no effect on the caffeine-induced contraction in the artery segments, indicating the inhibition of intracellular Ca2+ release as a result of atropine most likely occurs via the IP3 pathway rather than the ryanodine receptors. Our results suggest that atropine-induced vasodilatation is mainly from artery smooth muscle cells due to inhibition of the receptor-mediated Ca2+-influx and Ca2+-release, and partly from the endothelium mediated by EDHF.
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- Hansen-Schwartz, J, et al.
(författare)
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Subarachnoid hemorrhage-induced upregulation of the 5-HT1B receptor in cerebral arteries in rats
- 2003
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 99:1, s. 115-120
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Tidskriftsartikel (refereegranskat)abstract
- Object. Cerebral vasospasm following subarachnoid hemorrhage (SAH) leads to reduced blood flow in the brain. Inspired by organ culture-induced changes in the receptor phenotype of cerebral arteries, the authors investigated possible changes in the 5-hydroxytryptamine (HT) receptor phenotype after experimental SAH. Methods. Experimental SAH was induced in rats by using an autologous prechiasmatic injection of arterial blood. Two days later, the middle cerebral artery (MCA), posterior communicating artery (PCoA), and basilar artery (BA) were harvested and examined functionally with the aid of a sensitive in vitro pharmacological method and molecularly by performing quantitative real-time reverse transcription-polymerase chain reaction (PCR). In the MCA and BA the 5-HT1B receptor was upregulated, as determined through both functional and molecular analysis. In response to selective 5-HT1 receptor agonists both the negative logarithm of the 50% effective concentration was increased (one log unit in the MCA and one half unit in the BA), as was the agonist's potency (increased by 50% in the MCA and doubled in the BA). In addition, the authors found an approximately fourfold increase in the number of copies of messenger RNA coding for the 5-HT1B receptor as determined by quantitative real-time PCR. In the PCoA no upregulation of the 5-HT1B receptor was observed. Conclusions. Changes in the receptor phenotype in favor of contractile receptors may well represent the end stage in a sequence of events leading from SAH to the actual development of cerebral vasospasm. Insight into the mechanism of upregulation may provide new targets for developing specific treatment against cerebral vasospasm.
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- Ren, J, et al.
(författare)
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Expression of sphingosine kinase gene in the interactions between human gastric carcinoma cell and vascular endothelial cell
- 2002
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Ingår i: World Journal of Gastroenterology. - 1007-9327. ; 8:4, s. 602-607
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the interactions between human gastric carcinoma cell (HGCC) and human vascular endothelial cell (HVEC), and if the expression of sphingosine kinase (SPK) gene was involved in these interactions. METHODS: The specific inhibitor to SPK, dimethyl sphingosine (DMS), was added acting on HGCC and HVEC, then the cell proliferation was measured by MTT. The conditioned mediums (CMs) of HGCC and HVEC were prepared. The CM of one kind of cell was added to the other kind of cell, and the cell proliferation was measured by MTT. After the action of CM, the cellular expression of SPK gene in mRNA level was detected with in situ hybridization (ISH). RESULTS: DMS could almost completely inhibit the proliferation of HGCC and HVEC. The growth inhibitory rates could amount to 97.21%, 83.42%, respectively (P<0.01). The CM of HGCC could stimulate the growth of HVEC (2.70 +/- 0.01, P<0.01) while the CM of HVEC could inhibit the growth of HGCC (52.97 +/- 0.01%, P<0.01). There was no significant change in the mRNA level of SPK gene in one kind of cell after the action of the CM of the other kind of cell. CONCLUSION: SPK plays a key role in regulating the proliferation of HGCC and HVEC. There exist complicated interactions between HGCC and HVEC. HGCC can significantly stimulate the growth of HVEC while HVEC can significantly inhibit the growth of HGCC. The expression of SPK gene is not involved in the interactions.
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- Ren, J, et al.
(författare)
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The role of KDR in the interactions between human gastric carcinoma cell and vascular endothelial cell
- 2002
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Ingår i: World Journal of Gastroenterology. - 1007-9327. ; 8:4, s. 596-601
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Tidskriftsartikel (refereegranskat)abstract
- AIM:To study the interactions between human gastric carcinoma cell (HGCC) and human vascular endothelial cell (HVEC), and the role of KDR in these interactions. METHODS:Antisense oligodexynucleotide(ASODN) specific to KDR gene was devised and added to the culture medium of HGCC and HVEC. After the action of ASODN, the proliferation of two cells was measured by MTT method. The role of KDR in regulating the proliferation of two kinds of cells was known through observing the effect of ASODN on them. The conditioned mediums (CMs) of HGCC and HVEC were prepared. The CM of one kind of cell was added acting on the other kind of cell, then the cell proliferation was measured by MTT. After the action of ASODN or CM, the cellular expression of KDR gene was detected with in situ hybridization(ISH) for mRNA level and with immunohistochemical staining for protein level. ABC-ELISA was used to detect hVEGF in the CMs of two cells. RESULTS: KDR ASODN could specifically inhibit the proliferation of HGCC and HVEC significantly. The growth inhibitory rate amounted to 55.35 % and 54.83 %, respectively (P <0.01). HGCC and HVEC could secret a certain level of hVEGF(92.06 +/- 1.69 ng/L, 77.70 +/- 8.04 ng/L. The CM of HGCC could significantly stimulate the growth(2.70 +/- 0.01 times) and KDR gene expression of HVEC( P<0.01) while the CM of HVEC could significantly inhibit the growth(52.97 +/- 0.01%) and KDR gene expression of HGCC (P <0.01). CONCLUSION: KDR plays a key role in regulating the proliferation of HGCC and HVEC. There exist complicated interactions between HGCC and HVEC. HGCC can significantly stimulate the growth of HVEC while HVEC can significantly inhibit the growth of HGCC. KDR is involved in the interactions between them.
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