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ABSTRACT: The protein encoded by adenomatous polyposis coli (APC) gene participates in the signaling transduction pathway. Substantial studies have revealed that hypermethylation of APC gene promoter is closely related to the pathogenesis and development of cancer. This study was to develop a real-time quantitative methylation specific PCR (real-time QMSP) method, and detect the methylation of APC gene promoter in plasma of lung cancer patients.
Genomic DNA with methylated APC gene promoter was extracted from the lung cancer cell line NCI-H460 using phenol-chloroform and quantified by spectrophotometric measurements. DNA was added into 200 microL plasma samples of healthy volunteers to make 10-fold serial dilutions. Circulating DNA from simulated plasma samples, 78 lung cancer patients, 31 patients with benign lung diseases and 23 health controls was extracted using magnetic beads and modified by bisulfite. The concentration of cell-free methylated APC gene promoter in the plasma samples was quantified by the external reference method with the standard curve constructed using simulated plasma.
The linear range of the real-time QMSP assay was 1.5x10(2)-1.5x10(5) copies/ mL and its lowest detectability was 1.5x10(2) copies per milliliter plasma. Of 78 lung cancer patients, positive methylation of the APC gene promoter was detected in tumor tissues of 40 cases. Among the 40 lung cancer patients, positive methylation of the APC gene promoter was found in the plasma of 19 patients (47.5%). The concentrations of methylated APC promoter in the 19 lung cancer patients ranged from 1.67x10(2) to 6.78x10(3) copies/mL, with a median concentration of 1.67x10(3) copies/mL. No positive methylation of the APC gene promoter was detected in the plasma of 38 lung cancer patients without APC gene methylation in tissues, 31 benign lung diseases and 23 healthy controls.
The newly developed real-time QMSP method allows the quantitative measurement of APC gene promoter methylation in plasma. Hypermethylation of the APC gene promoter in plasma is a potential diagnostic marker for lung cancer diagnosis.
Ai zheng = Aizheng = Chinese journal of cancer 05/2009; 28(4):384-9.
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Chinese medical journal 02/2008; 121(1):78-81. · 0.86 Impact Factor
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ABSTRACT: Although astragaloside IV, a saponin isolated from Astragalus membranaceus, has been shown to protect the myocardium against ischemia/reperfusion injury, its effect on the status of sarcoplasmic reticulum (SR) Ca2+ transport in the injured myocardium remains largely unknown. In this study, we investigated whether in cultured cardiomyocytes subjected to hypoxia and reoxygenation (H/R) administration of astragaloside IV during H/R attenuates the myocardial cell injury and prevents changes in Ca2+ handling activities and gene expression of SR Ca2+ pump. Cultured cardiomyocytes from neonatal rats were exposed to 6 h of hypoxia followed by 3 h of reoxygenation. Myocyte injury was determined by the release of cardiac troponin I in supernatant. Astragaloside IV significantly inhibited cardiac troponin I release after H/R in a dose-dependent manner. The diastolic [Ca2+]i measured with Fura-2/AM was significantly increased after reoxygenation. Astragaloside IV prevented the rise of diastolic [Ca2+]i and the depression of caffeine-induced Ca2+ transients caused by H/R. Furthermore, the observed depressions in SR Ca2+-ATPase activity as well as the mRNA and protein expression of SR Ca2+-ATPase in hypoxic-reoxygenated cardiomyocytes were attenuated by astragaloside IV treatment. These results suggest that the beneficial effect of astragaloside IV in H/R-induced injury may be related to normalization of SR Ca2+ pump expression and, thus, may prevent the depression in SR Ca2+ handling.
Pharmacology 02/2008; 81(4):325-32. · 1.79 Impact Factor
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ABSTRACT: To assess the parameters of cardiac structure and function of male Balb/c mice by the echocardiography.
A total of 27 male Balb/c mice (from five to seven week old) were examined with a 13-MHz transthoracic linear-array transducer, hearts were removed from mice anesthetized with Nembutal, and the left ventricular (LV) mass were weighed.
Complete 2-dimensional echocardiography for cardiac structure and function were obtained. Hemodynamic parameters were recorded. A correlation existed between LV weight (x) and echocardiographic LV mass (y) with the 2D) guided M-mode method: y = 1.15x + 3.26, (r = 0.80).
Echocardiography appears to be a promising approach for noninvasively assessing LV mass and function in mice.
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 11/2007; 23(4):390-3.
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ABSTRACT: The cardiovascular pre-participation screening proposal for young competitive athletes has the potential to save young lives. This study aimed to identify individuals at risk for potentially lethal cardiovascular diseases in athletes before competition. Between June 2005 and July 2005, 351 (170 male and 181 female) elite Chinese athletes from 21 sports were profiled. The 12-lead electrocardiogram and echocardiography were employed to evaluate cardiovascular diseases. The vast majority had no definitive evidence of cardiovascular disease. However, abnormal ECGs were identified in 16 athletes (4.5%), including 4 with distinctly abnormal and 12 with mildly abnormal patterns. Only 13 athletes (3.7%) had echocardiographic evidence of relatively mild valve regurgitation that had not been previously suspected. In three athletes with relatively mild ventricular septal hypertrophy (13-14 mm), it was not possible to discern with absolute certainty whether the wall thickening was a manifestation of hypertrophic cardiomyopathy or secondary to athletic conditioning ("athlete heart"). This screening protocol identified no athletes with definite evidence of hypertrophic cardiomyopathy, Marfan's syndrome or other cardiovascular diseases that convey a significant potential risk for sudden death or disease progression during athletic activity. This is largely due to the relative low prevalence of conditions resulting in sudden cardiac death in young athletes and high false positive/negative rates in the tests used as part of the screening process (due to a large overlap between cardiovascular changes due to pathology and those due to intense training).
Journal of Science and Medicine in Sport 09/2007; 10(4):227-33. · 3.03 Impact Factor
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ABSTRACT: Hypermethylation of CpG islands in adenomatous polyposis coli (APC) gene has been detected in a variety of human tumors, which is involved in the pathogenesis of these tumors. In previous research, we detected APC promoter methylation in 47% lung tumor tissues. This study was to analyze the effect of APC promoter methylation on the gene transcription in 3 lung cancer cell lines.
The methylation status of APC promoter 1A in lung adenocarcinoma cell line SPCA1, small cell lung cancer cell line NCI-H446, and big cell lung cancer cell line NCI-H460 was detected by methylation-specific polymerase chain reaction (MSP) and microarray methylated cord blood DNA served as positive control, and unmethylated cord blood DNA served as negative control. The expression of APC was examined by real-time quantitative polymerase chain reaction (PCR) with Sybr-Green I staining. After treatment of 1, 5, 10, 15 micromol/L DNA methyltransferase inhibitor 5-aza-2-deoxycytidine (5-aza-dC), the expression of APC in NCI-H460 cells was detected by real-time PCR.
APC promoter 1A was methylated in NCI-H460 cells, and unmethylated in NCI-H446 and SPC-A1 cells. Hypermethylation was detected in all 5 CpG islands (687, 707, 714, 719, 726) of APC promoter 1A in NCI-H460 cells. The expression of APC in NCI-H460 cells was decreased by 26.04% of that in NCI-H446 cells and by 32.36% of that in SPCA1 cells. After treatment of 1, 5, 10, 15 micromol/L 5-aza-dC, the expression of APC promoter 1A in NCI-H460 cells was enhanced by 4.59, 5.78, 9.58, 5.98 folds, respectively.
APC gene is hypermethylated in HCI-H460 cells, and its transcription coud be activated by 5-aza-dC.
Ai zheng = Aizheng = Chinese journal of cancer 06/2007; 26(6):576-80.
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ABSTRACT: Dysregulation of intracellular Ca2+ homeostasis plays an important role in mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve intracellular Ca2+ handling in myocardial injury of rats. The control group received saline only (10 ml kg(-1) day(-1), i.p.) for 7 days. In a second group, isoprenaline (ISO; 5 mg kg(-1) day(-1), s.c.) was administered to rats for 2 days to induce an acute injury of the myocardium. In a third group, treatment with TMZ (10 mg kg(-1) day(-1), i.p.) was initiated 1 day before ISO administration and continued for 7 days (n = 7 rats in each group). Histopathological evaluation showed that TMZ prevented ISO-induced myocardial damage. TMZ preserved the ATP levels and decreased the maleic dialdehyde (MDA) content in the hearts compared with ISO-treated rats. The diastolic [Ca2+]i measured by loading with fura-2 AM in isolated cardiomyocytes was increased significantly in ISO-treated rats compared to the control animals. TMZ prevented the rise of diastolic [Ca2+]i and the depression of caffeine-induced Ca2+ transients caused by ISO administration. The reduction in sarcoplasmic reticulum (SR) Ca2+ content in the heart cells and in cardiac SR Ca2+-ATPase activity in ISO-treated rats was abolished by TMZ, although there were no differences in SR Ca2+-ATPase protein levels between the control, ISO and ISO + 7 mz-treated rats. In addition, TMZ prevented the reduction in sarcolemmal L-type Ca2+ current density in the heart cells induced by ISO treatment. These results demonstrate that the treatment of rats with TMZ inhibited the increase of diastolic [Ca2+]i and prevented the decrease of SR Ca2+ content, SR Ca2+-ATPase activity and L-type Ca2+ current density in cardiomyocytes in ISO-mediated myocardial injury of rats. These changes in Ca2+ handling could help to explain the favourable action of TMZ in myocardial injury.
Experimental Physiology 05/2006; 91(3):591-601. · 3.21 Impact Factor
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Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 04/2006; 34(3):197-200.
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ABSTRACT: We have extracted and roughly purified astragalosides (AS) from Astragalus membranaceus, a natural herb used as a traditional Chinese medicine, regarded to have pharmacodynamic benefits of protecting injured myocardium. We hypothesized that the astragalosides might exert beneficial effect in myocardial lesion by preserving both energy metabolism and Ca(2+) homeostasis. Sprague-Dauley (SD) rats were injected with isoproterenol (ISO) subcutaneous (s.c.) at a dose of 5 mg/kg/day consecutively for two days as models and were treated with astragalosides and trimetazidine intraperitoneally (i.p.) respectively, at a dose of 5 mg/kg/day one day prior to isoproterenol for 8 days. The histological changes were alleviated in isoproterenol-injected SD rats treated with astragalosides. Compared with isoproterenol-injected rats, the concentration of myocardial intracellular [Ca(2+)]i was decreased, L-type Ca(2+) current density and sarcoplasmic reticulum (SR) Ca(2+) load were recovered, the concentration of myocardial ATP was increased and phosphocreatine (PCr) was decreased in rats treated with astragalosides. In conclusion, the efficacious treatment of astragalosides for myocardial injury might be through regulating intracellular Ca(2+) homeostasis and energy metabolism.
The American Journal of Chinese Medicine 02/2006; 34(6):1015-25. · 1.98 Impact Factor
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ABSTRACT: In clinical practice, Astragali Radix (Astragalus), the root of Astragalus membranaceus Bunge, has been widely applied to treat patients with viral diseases, including viral myocarditis in China. The present study was designed to evaluate the protective effects of Astragalus on the function of sarcoplasmic reticulum calcium ATPase (SERCA2) activity and endothelin system at acute and chronic periods of myocarditis mice induced by CVB(3) infection. Astragalus feeding (2.2 mg/kg/day) could significantly increase the survival rate, alleviate pathological alterations and serum cardiac troponin I (cTnI), as well as restore impaired SERCA activity at the acute stage. Low affinity and capacity of ETR were reversed with Astragalus after the first CVB(3) inoculation up to 7 days and after the second virus inoculation up to 150 days. In the meantime, the contents of cardiac ET-1 and ANP were reduced. Comparison the myocarditis mice treated with Perindopril (0.44 mg/kg/day), an ACE inhibitor, shows that Astragalus achieved a similar effect on survival rate, SERCA2 and ET system. These results indicated that the beneficial effects of Astragalus and Perindopril for treating viral myocarditis might be partly mediated by preserving the functions of SERCA 2 activity and ET system.
The American Journal of Chinese Medicine 02/2006; 34(3):493-502. · 1.98 Impact Factor
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Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 07/2005; 33(6):491-4.
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ABSTRACT: Astragalosides were the main active components from a native Chinese herb Astragalus membranaceus. Recent studies have shown that Astragalosides have a protective effect on myocardial injury in rats. The present study was designed to investigate the effect of Astragalosides on intracellular calcium overload and sarcoplasmic reticulum calcium load (SR Ca2+ load) in cultured cardiac myocytes from neonatal rats. Astragalosides (100 microg/ml) were incubated in the presence of isoproterenol (ISO) (10(-5) M) for 72 hours in cardiomyocytes. Metoprorol (10(-6) M), a beta1-selective antagonist, was cultured in the same condition as Astragalosides. The result showed that intracellular calcium concentration ([Ca2+]i) and SR Ca2+ load increased in ISO-treated cardiac myocytes as compared to control (P < 0.01). Astragalosides prevented ISO-induced increase in [Ca2+]i and SR Ca2+ load. Metoprolol also inhibited those increase. The mRNA expression and activity of sarcoplasmic reticulum Ca2+ ATPase (SERCA) were enhanced following ISO treatment in cardiac myocytes, and these increases were inhibited by Astragalosides or metoprolol (P < 0.05). The decrease of superoxide dismutase (SOD) activity and the elevation of intracellular maleic dialdehyde (MDA) were observed after ISO treatment in cardiac myocytes. Both Astragalosides and metoprolol restored the SOD activity and reduced the level of MDA. We conclude that Astragalosides have the effects on reducing [Ca2+]i and SR Ca2+ load, enhancing free radical removal and decreasing lipid peroxidation in ISO-treated cardiomyocytes, which might account for their protective effect on myocardial injury.
The American Journal of Chinese Medicine 01/2005; 33(1):11-20. · 1.98 Impact Factor
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Chinese medical journal 07/2004; 117(6):944-6. · 0.86 Impact Factor
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ABSTRACT: In the aorta of the spontaneously hypertensive rat (SHR), endothelium-dependent contractions are enhanced by inhibitors of NO synthase and scavengers of NO, but not by methylene blue, an inhibitor of guanylyl cyclase, suggesting that the endothelium-derived contracting factor (EDCF) interacts chemically with NO and is inactivated by the latter. However, in view of the relative lack of specificity of methylene blue this hypothesis was re-examined. Acetylcholine-induced endothelium-dependent contractions of isolated rings of SHR aorta were significantly and similarly potentiated by two NOS inhibitors, by two structurally different NO scavengers, by two inhibitors of guanylate cyclase ODQ and NS2028, but to a lesser extent by methylene blue. The contraction of the isolated rat trachea in response to methacholine and the contraction of the rat aorta in response to both 8-isoprostane and KCl were inhibited significantly by methylene blue. Methylene blue binds to the M3 muscarinic receptor subtype but not to the TP receptor. Therefore, methylene blue is an antagonist of the M3 muscarinic receptor subtype, involved in the release of EDCF, and a non-specific inhibitor of TP receptor-mediated contractions, the receptor involved in the action of EDCF. These inhibitory effects of methylene blue are likely to counteract the effect of the inhibition of soluble guanylate cyclase. These results rule out the hypothesis according to which NO would chemically inactivate EDCF.
Journal of Cardiovascular Pharmacology 07/2004; 43(6):815-20. · 2.29 Impact Factor
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ABSTRACT: The present study was designed to determine whether or not an increase in endothelial intracellular concentration of calcium ([Ca2+]i) evokes endothelium-dependent contractions in the aorta from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Acetylcholine, adenosine triphosphate (ATP) and the calcium ionophore, A 23187, produced endothelium-dependent relaxations in isolated aortic rings of both WKY and SHR. These relaxations in response to the three agonists were significantly smaller in the SHR when compared with the WKY. Endothelium-dependent contractions to acetylcholine, ATP and A 23187 were observed only in the aorta isolated from the SHR. In the presence of NG-nitro-L-arginine, an NO synthase inhibitor, the endothelium-dependent contractions in response to acetylcholine, ATP and A 23187 were potentiated significantly in the aorta SHR and were unmasked in that of WKY. However, the contractions were still significantly greater in SHR than in WKY. These contractions were abolished by indomethacin and valeryl salicylate (two cyclo-oxygenase inhibitors) as well as by S 18886 (a TP-receptor antagonist), indicating that the endothelium-dependent contraction produced by the three agonists share the same characteristics. The results of the present study indicate that the release/generation of endothelium-derived contracting factor, requires an increase in endothelial [Ca2+]i.
Fundamental and Clinical Pharmacology 07/2004; 18(3):321-6. · 1.80 Impact Factor
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ABSTRACT: To investigate the changes of cardiac calcium handling proteins and endothelin system in dilated cardiomyopathy (DCM) rats and the effects of perindopril and bisoprolol on the remodeling ventricles.
DCM rats were employed using a 2-kidney, 1-clip hypertensive and diabetic model. Some of the DCM rats were treated with perindopril and bisoprolol for 3 months, respectively. The ratio of left ventricular weight to body weight (LVW/BW), mRNA expressions of calcium handling proteins and endothelin receptors were determined. The alterations of maximum binding capacity (Bmax) and equilibrium dissociation constant (KD) values of cardiac endothelin receptors (ETR) and its subtypes were detected.
Compared with those of normal control, blood pressure, and LVW/BW in the DCM rats were elevated. Sarcoplasmic reticulum calcium pump (SERCA) mRNA expression and SERCA activity decreased in the left ventricle. The ETR Bmax decreased, especially the endothelin receptor A. Endothelin converting enzyme activity and expression were elevated, and mRNA expressions of beta1-adrenoreceptor and inositol-3-phosphate receptor in some hearts increased as well. The administration of perindopril and bisoprolol could reverse myocardial hypertrophy and restore the imbalance of calcium handling proteins and endothelin system.
The disorder of calcium handling proteins and endothelin system existed in the hearts of DCM rats. Treatment of perindopril and bisoprolol could reverse myocardial hypertrophy and changes in DCM rats.
Acta Pharmacologica Sinica 12/2003; 24(11):1099-102. · 1.95 Impact Factor
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ABSTRACT: The present study was to investigate the mRNA, protein expression and the activity of calcineurin in the hypertrophic heart, and to determine the effect of calcineurin inhibitor--cyclosporine A (CsA) on the regression of cardiac hypertrophy in renovascular hypertensive rats. Renovascular hypertension was induced by two kidney-one clip methods. Two months after the operation, cardiac hypertrophy was determined by histological analysis performed in some rats (2K1C-2M), then the rats were subdivided into 2 groups: (1) 3-month old two kidney-one clip group (2K1C-3M) with rats receiving 0.9% NaCl per day for one month, and (2) CsA-treated group with rats treated with CsA for one month. Sham-operated rats were used as control. The ratio of the left ventricular weight to tibial length (LVW/TL), the area of cardiac myocyte, mRNA and protein expression and the activity of calcineurin were determined. Both the LVW/TL and the cardiomyocyte area were significantly larger in 2K1C-2M and 2K1C-3M rats than in age-matched sham-operated rats. Treatment with CsA significantly attenuated the increase in the LVW/TL as well as the cardiomyocyte area. The mRNA, protein expression and the activity of calcineurin were significantly higher in 2K1C-2M and 2K1C-3M rats than those in the age-matched sham-operated rats, while the elevation of mRNA, protein expression and activity of calcineurin were significantly suppressed in the CsA-treated rats. In conclusion, calcineurin plays a role in the progression of cardiac hypertrophy in renovascular hypertensive rats. The inhibition of calcineurin can reverse cardiac hypertrophy.
Sheng li xue bao: [Acta physiologica Sinica] 11/2003; 55(5):594-8.
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ABSTRACT: This study was designed to determine the effect of pteridines, R- and S-tetrahydrobiopterin, sepiapterin, and dihydrobiopterin on endothelium-dependent contractions to acetylcholine in isolated aortas from spontaneously hypertensive rat and normotensive Wistar-Kyoto rat. The noncumulative addition of redox-active pteridines R- and S-tetrahydrobiopterin (but not the oxidized analogues sepiapterin and dihydrobiopterin) produced a concentration-dependent transient contraction in isolated aortic rings from both normotensive and hypertensive rats. R- and S-tetrahydrobiopterin (but not sepiapterin or dihydrobiopterin) potentiated the endothelium-dependent contractions to acetylcholine but only in aortas from hypertensive rats and in the presence of N(G)-nitro-L-arginine. In these aortas, the generation of oxygen-derived free radicals by the combination of xanthine plus xanthine oxidase also potentiated the endothelium-dependent contractions to acetylcholine. The presence of R-tetrahydrobiopterin did not alter the characteristics of the endothelium-dependent contractions because they were inhibited by valeryl salicylate, an inhibitor of cyclooxygenase-1, by S18886, a TP-receptor antagonist or by Tiron, a cell permeable superoxide anion scavenger. However, the contractions to acetylcholine, which are unaffected by the combination of superoxide dismutase and catalase, become significantly inhibited by these two scavengers in the presence of R-tetrahydrobiopterin. In the presence of N(G)-nitro-L-arginine, R-tetrahydrobiopterin did not affect the contractions to phenylephrine, U 46619, or to oxygen-derived free radicals generated by xanthine plus xanthine oxidase. These results indicate that the production of superoxide by the autoxidation of tetrahydrobiopterin selectively enhances endothelium-dependent contractions in the spontaneously hypertensive rat when nitric oxide synthase is inhibited.
Hypertension 02/2003; 41(1):136-42. · 6.21 Impact Factor
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ABSTRACT: A modified bioassay system was designed to demonstrate the diffusible nature of endothelium-derived contracting factor(s) released by acetylcholine in the aorta of spontaneously hypertensive rat. In "sandwich"-like layered preparation, isometric tension was recorded from a bioassay strip (without endothelium) in the presence of N(G)-nitro-L-arginine and tetrahydrobiopterin to selectively potentiate endothelium-dependent contractions. A donor strip (with or without endothelium) was stitched on the bioassay tissue so that it did not directly contribute to the recorded contractions. Acetylcholine induced contractions that occurred only when the donor strip was with endothelium. Superoxide dismutase did not affect but catalase and the combination of superoxide dismutase plus catalase significantly decreased the endothelium-dependent contraction. The contractions in the layered preparations were abolished when the donor strip with endothelium was treated previously with valeryl salicylate, an irreversible cyclooxygenase-1 inhibitor, but remained unaffected when the bioassay strip was treated with the compound. Previous treatment of the bioassay strip alone with S 18886 abolished the contractile response, whereas treatment of the donor strip with endothelium by the selective TP receptor antagonist only produced a moderate inhibition. These results indicate that in the aorta of spontaneously hypertensive rats, endothelium-dependent contractions to acetylcholine involve a diffusible substance(s) released by the endothelium. The production of this contracting factor(s) requires the activation of endothelial cyclooxygenase-1, and its action the activation of TP receptors on the vascular smooth muscle cells.
Hypertension 02/2003; 41(1):143-8. · 6.21 Impact Factor
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ABSTRACT: Experiments were designed to investigate whether or not oxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rat (SHR). Isometric tension was measured in aortic rings taken from adult male SHR and Wistar-Kyoto rat (WKY) in the presence of NG-nitro-L-arginine. Endothelium-dependent contractions to acetylcholine were significantly greater in rings from SHR compared to WKY. Oxygen-derived free radicals, generated from xanthine plus xanthine oxidase, induced contractions that were larger in aortas from SHR than from WKY. Contractions to acetylcholine and free radicals were abolished by a selective TP-receptor antagonist, S 18886, and a preferential inhibitor of cyclo-oxygenase-1, valeryl salicylate, but not by a preferential inhibitor of cyclo-oxygenase-2, NS-398. Allopurinol, deferoxamine and the combination of superoxide dismutase plus catalase inhibited the contractions to oxygen-derived free radicals but did not significantly affect those to acetylcholine. In contrast, diethyldithiocarbamic acid, an inhibitor of superoxide dismutase, or Tiron, a scavenger of superoxide anion, reduced endothelium-dependent contractions to acetylcholine in aortas from SHR. The effect of these two drugs was additive. In SHR chronically treated with dimethylthiourea endothelium-dependent contractions to acetylcholine were decreased, and reduced further by acute in vitro exposure to deferoxamine or the combination of superoxide dismutase plus catalase. These results suggest that in the SHR aorta acetylcholine-induced endothelium-dependent contractions involve endothelial superoxide anion production and the subsequent dismutation into hydroxyl radicals and/or hydrogen peroxide. The free radicals activate cyclo-oxygenase-1, most likely to produce endoperoxides. Activation of TP-receptors is required to observe endothelium-dependent contractions to acetylcholine or endothelium-independent contractions in response to free radical generation.
British Journal of Pharmacology 06/2002; 136(1):104-10. · 4.41 Impact Factor
