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931.
932.
目的 研究氯沙坦对原发性高血压(EH)患者血管内皮功能的影响.方法 分析应用氯沙坦前后EH患者血压、ET(血浆内皮素)及NO(一氧化氮)的变化.结果 EH患者血浆ET升高(P<0.01)、NO降低(P<0.01).应用氯沙坦后,EH患者血压显著下降(P<0.01)、ET明显降低(P<0.01),NO明显升高(P<0.01).结论 氯沙坦可有效降压,并能逆转EH患者血管内皮功能紊乱. 相似文献
933.
目的 探讨针刺水沟-风府穴组治疗缺血性脑卒中的作用机制。方法 将40只大鼠分为正常组、模型组、水沟-风府组(针刺大鼠水沟、风府穴)、非经非穴组(针刺大鼠臀部两处非经非穴点),每组10只。采用阻闭大鼠大脑中动脉制备永久性脑缺血模型。72 h后观察各组大鼠神经功能评分,血清一氧化氮及血浆内皮素含量的变化。结果 与模型组比较,水沟-风府组脑缺血大鼠神经功能评分明显降低(P<0.05),而非经非穴组无明显变化(P>0.05)。与模型组比较,非经非穴组大鼠血清一氧化氮及血浆内皮素含量无明显变化(P>0.05),水沟-风府组大鼠血清一氧化氮及血浆内皮素含量明显降低(P<0.05)。结论 针刺水沟-风府穴组对缺血性脑卒中具有明显的改善作用,其机制可能与降低血液中一氧化氮、内皮素的含量有关。 相似文献
934.
目的 分析不同剂量阿托伐他汀对H型高血压患者同型半胱氨酸(Hcy)、内皮功能和C反应蛋白(CRP)的影响.方法 将120例H型高血压患者分为常规治疗组、强化治疗组和对照组,每组40例.3组患者均给予常规降压治疗,常规治疗组和强化治疗组在常规降压治疗基础上分别口服阿托伐他汀20 mg/d和40 mg/d,治疗12周.观察治疗前后患者血脂水平、血压、血清Hcy、内皮素-1(ET-1)、C-反应蛋白(CRP)、NO水平变化.结果 治疗后,常规治疗组和强化治疗组血压较前下降(P<0.05),血脂水平较前改善(P<0.05),血清Hcy、ET-1、CRP、NO水平均下降(P<0.05),并且Hcy、ET-1、CRP及NO水平下降水平高于对照组(P<0.05);强化治疗组Hcy、ET-1、CRP及NO下降水平高于常规治疗组(P<0.05).结论 大剂量阿托伐他汀能够降低H型高血压患者血清Hcy水平,抑制炎症反应,改善内皮功能,提高疗效. 相似文献
935.
Alexander Treiber Tommaso Miraval Martin H. Bolli Jacques-Alexis Funel Jerome Segrestaa Swen Seeland 《Xenobiotica; the fate of foreign compounds in biological systems》2016,46(3):253-267
Abstract1.?The metabolism of the endothelin receptor antagonist macitentan has been characterized in bile duct-cannulated rats and dogs.2.?In both species, macitentan was metabolized along five primary pathways, i.e. conjugation with glucose (M9), oxidative depropylation (M6), aliphatic hydroxylation (M7), oxidative cleavage of the ethylene glycol linker (M4) and hydrolysis of the sulfamide moiety (M3). Most of the primary metabolites underwent subsequent biotransformation including conjugation with glucuronic acid or glucose, hydrolysis of the sulfamide group or secondary oxidation of the ethylene glycol moiety.3.?Though there were species differences in their relative importance, all metabolic pathways were present in rat and dog. The depropylated M6 was the only metabolite present in plasma of both species.4.?Metabolism was a prerequisite for macitentan excretion as relevant amounts of parent drug were neither detected in bile nor urine. Biliary excretion was the major elimination pathway, while renal elimination was of little importance. 相似文献
936.
Kavanagh M Seaborn T Crochetière J Fournier L Battistini B Piedboeuf B Major D 《Journal of pediatric surgery》2005,40(9):1382-1389
Background/Purpose
Previously, we reported that perinatal administration of atrasentan, a selective endothelin A receptor (ETA) antagonist, provided a beneficial effect on the cardiopulmonary profile under short-term conditions in newborn lambs with surgically induced congenital diaphragmatic hernia (CDH). We hypothesized that changes in the hemodynamic profile that we observed at birth in treated animals could be influenced by pulmonary modulation of the endothelin (ET) system.Methods
The effect of atrasentan on protein expression levels of ETs and ET receptors (ETA and ETB receptor) was investigated by immunohistochemistry in lung tissues of untreated control (n = 3), treated control (n = 6), untreated CDH (n = 6), and treated CDH newborn lambs (n = 8).Results
Right lung tissue of treated control lambs showed significantly higher ETA protein expression levels in both vascular adventitia and airway epithelia when compared with that of untreated control lambs (P < .05). In contrast, protein expression levels of ETA and ET B receptor were significantly lower in the vascular smooth muscle cells among other tissue subcompartments of the right lung of treated CDH newborn lambs vs CDH lambs (P < .02 and P = .005, respectively).Conclusions
We speculate that rapid pulmonary modulation of ET system protein expression levels by atrasentan results from an indirect effect possibly dependent on ventilation and/or perfusion. In CDH groups, this could contribute to the beneficial effect of the treatment. 相似文献937.
Daray FM Colombo JR Kibrik JR Errasti AE Pelorosso FG Nowak W Cracowski JL Rothlin RP 《Naunyn-Schmiedeberg's archives of pharmacology》2006,373(5):367-375
The present study was undertaken to evaluate the contractile response of several E- and F-ring isoprostanes (IsoP) in human umbilical vein (HUV) and to investigate the role of the endothelium on the effect of 15-E2t-IsoP, the most potent vasoconstrictor isoprostane, in human vessels. HUV rings with or without endothelium were suspended in an organ bath for recording the isometric tension in response to different agonists. The inhibitors to be evaluated were applied 30 min before the addition of the agonist. All of the compounds tested produced concentration-dependent contractions when tested on HUV rings with endothelium. Although these compounds were equieffective, significant differences were observed in their potency, with U46619 being the most potent followed by 15-E2t-IsoP > 15-E1t-IsoP = 15-F2t-IsoP > 15-F1t-IsoP = 9-epi-15-F2t-IsoP in descending rank order of potency. 15-E2t-IsoP was the most potent of the isoprostanes evaluated and, therefore, the one employed in the present study. When intact endothelium HUV rings were used, 15-E2t-IsoP-induced contraction was unaffected by the endothelin-converting enzyme inhibitor, phosphoramidon (10 μM), suggesting that short-term endothelin-1 release is not involved in this response. However, the non-selective cyclooxygenase (COX) inhibitor, indomethacin (10 and 30 μM), and the COX-2 selective inhibitor, NS-398 (3, 10 and 30 μM) produced inhibitory effects on 15-E2t-IsoP-induced contraction of HUV rings with endothelium. These results indicate that COX-derived contractile prostanoids are involved in this effect. Furthermore, the apparent pK
b values estimated for indomethacin (5.5) and NS-398 (5.4) suggest that the prostanoids involved are derived from the COX-2 isoenzyme pathway. On HUV rings with endothelium, the phospholipase A2 inhibitor, oleyloxyethyl phosphorylcholine (30 and 100 μM), induced an inhibitory effect on 15-E2t-IsoP-induced contraction, suggesting that the phospholipase A2 pathway is also involved in this effect. In addition, the thromboxane A2 synthase inhibitor furegrelate (10 and 30 μM) also inhibited 15-E2t-IsoP-induced contraction of HUV rings with endothelium, indicating that thromboxane A2 is one of the contractile prostanoids involved in this response. Endothelium denudation clearly diminished the vasoconstrictor potency of 15-E2t-IsoP, demonstrating that the endothelium releases a vasoconstrictor factor in response to 15-E2t-IsoP. The absence of an inhibitory effect at the highest concentration of furegrelate (30 μM) on 15-E2t-IsoP-induced contraction of HUV rings without endothelium suggested that endothelium is the source of thromboxane A2. We conclude that prostanoids derived from the COX-2 isoenzyme pathway participate in 15-E2t-IsoP-induced vasoconstriction of isolated HUV rings. Our results also indicate that endothelial thromboxane A2 is one of the prostanoids involved in this effect. 相似文献
938.
Endothelin-converting enzyme-1-mediated signaling in adult rat ventricular myocyte contractility and apoptosis during sepsis 总被引:2,自引:0,他引:2
We hypothesized that modulation of endothelin-converting enzyme-1 (ECE-1) activity would affect phosphorylation of p38-mitogen activated protein kinase (p38-MAPK) and potentiate apoptosis in adult rat ventricular myocytes (ARVMs) during sepsis. The activity of ECE-1 in ARVMs was altered by increasing the substrate availability for ECE-1 by exogenous administration of bigendothelin-1 (bigET-1, 100 nM) and by inhibiting ECE-1 using FR901533 (10 microM) for 24-h. FR901533 significantly decreased the concentration of ET-1 in both sham and sepsis groups. FR901533 decreased p38-MAPK phosphorylation in sepsis but not in sham group. BigET-1 upregulated p38-MAPK phosphorylation, produced hypertrophy, decreased cell viability and reversed FR901533-induced down-regulation of p38-MAPK phosphorylation in both groups. Although, FR901533 did not affect cell cross-sectional area, it significantly reduced the viability of ARVM in both groups. The peak shortening of sham ARVMs was elevated by bigET-1, FR901533 and pretreatment with FR901533 followed by bigET-1. However, the contractility of septic ARVMs was not altered by either bigET-1 or FR901533 treatments per se. Septic ARVM exhibited significantly increased caspase-3 activity at 12 and 24-h. Pretreatment with FR901533 significantly elevated caspase-3 activity in both sham and sepsis group. The data demonstrated that bigET-1-induced hypertrophy in septic ARVM correlates with an ECE-1 dependent-activation of p38-MAPK. The results suggest that non-responsiveness of ARVM to bigET-1 is due to ECE-1 dependent apoptosis. We concluded that ECE-1 may play a crucial role in ARVM dysfunction via increased caspase-3 activity and p38-MAPK phosphorylation during sepsis. 相似文献
939.
Contribution of endogenous endothelin-1 to basal vascular tone during normal pregnancy and preeclampsia 总被引:1,自引:0,他引:1
Ajne G Ahlborg G Wolff K Nisell H 《American journal of obstetrics and gynecology》2005,193(1):234-240
OBJECTIVE: The aim of this study was to determine the physiologic role for endogenous endothelin in the regulation of vascular tone during normal pregnancy and preeclampsia. The vascular sensitivity to endothelin-1 during pregnancy was studied also. STUDY DESIGN: Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of phosphoramidon, an endothelin-converting enzyme inhibitor, for 60 minutes, which was followed by co-infusion with endothelin-1 for 30 minutes. Three groups were studied: healthy nonpregnant women, normal pregnant women, and women with preeclampsia. RESULTS: There was a significant increase in forearm blood flow in the nonpregnant group after phosphoramidon infusion alone (73%+/-37%; P<.05). Phosphoramidon did not change forearm blood flow in pregnant subjects. Co-infusion with endothelin-1 significantly decreased forearm blood flow in both the nonpregnant and normal pregnant women (53%+/-7% and 40%+/-11%, respectively; P<.01). No response to endothelin-1 was found among women with preeclampsia. CONCLUSION: The vascular sensitivity to endothelin-1 is not altered during normal pregnancy in contrast to preeclamptic pregnancy, where no effect of endothelin-1 was seen. Reduced endothelin dependence during pregnancy might be one mechanism behind the fall in peripheral vascular resistance. 相似文献
940.
卡托普利对自发性高血压大鼠微血管稀少和内皮功能障碍的影响 总被引:1,自引:0,他引:1
为探讨自发性高血压大鼠(SHR)的微血管改变和血管内皮细胞(VEC)功能障碍的关系及卡托普利(CPT)的干预效果,对9只SHR给予CPT(CPT组),并以10只WKY大鼠作为正常对照组(WKY组),以10只SHR作为实验纠(SHR组),观察检测人鼠的血压(BP)、回肠壁各级微动脉分支总数、血浆一氧化氮(NO)和血浆内皮素(ET)。结果显示,SHR组的微动脉分支总数、NO及K值[log(NO/ET)]均较WKY组下降(P均<0.01),而ET则增高(P<0.01);CPT组给药后第7口BP较给药前下降(P<0.01),其微动脉分支总数、NO及K值均较SHR组增加(P均<0.01);SHR的BP与K值呈负相关(r=-0.5863),BP与各级微动脉分支总数呈负相关(r=-0.7866~-0.6380),而K值与各级微动脉分支总数呈正相关(r=0.5951~0.7529)。认为SHR的微血管改变与其内皮功能状态关系密切,CPT时改善高血压的VEC功能和微血管稀少现象,从而发挥降压作用。 相似文献