心衰婴幼儿血浆内皮素和心钠素的变化及米力农对其的影响

目的了解婴幼儿充血性心力衰竭(CHF)时血浆内皮素(ET)和心钠素(ANP)的变化及米力农对其的影响。方法测定41例CHF婴幼儿静脉滴注米力农前后血浆ET和ANP的浓度,并与对照组40例健康婴幼儿比较分析。结果CHF婴幼儿血浆ET和ANP的浓度显著增高,静滴米力农后,血浆ET和ANP的浓度下降,与治疗前比较差异有统计学意义(P<0.01)。结论CHF婴幼儿血浆ET和ANP的浓度增高,应用米力农可降低ET和ANP的浓度。     

充血性心力衰竭患者血浆内皮素改变及卡托普利疗效分析

目的 :探讨内皮素 (ET)与充血性心力衰竭 (CHF)严重程度的关系及卡托普利对其影响。方法 :采用放射免疫法测定ET浓度。6 9例CHF患者为治疗组 (CHF组 ) ,30例正常人为对照组。 6 9例CHF患者中的 12例因有禁忌症而未用卡托普利治疗为非卡托普利组 ,余 5 7例常规口服卡托普利治疗为卡托普利组 ,测入院和治疗 4周时的ET。对随访资料完整的 4 2例卡托普利组患者分别于 8周和 12周时复查ET。结果 :CHF组与对照组比较 ,ET浓度明显增高 (P <0 0 1)。CHF组治疗 4周后ET都有降低 ,但卡托普利组降低明显 (P <0 0 5 )。在 8周与 12周时卡托普利组 4 2例患者ET浓度差异无显著性。结论 :ET参与了CHF的发生发展 ,血浆ET浓度和CHF严重程度呈正相关。血管紧张素转换酶抑制剂 (ACEI)卡托普利应用可降低血浆ET浓度。     

心血管系统内皮素B型受体研究进展

内皮素是迄今所发现的体内最强的缩血管物质,其与不同亚型的膜受体(包括内皮素受体A(endothelin receptor A,ETA)、B及C)结合后,产生不同甚至相反的病理生理效应。ETB受体主要参与内皮素的清除、血管舒张、水盐平衡,调节细胞增殖或凋亡,似乎作为"保护性受体"发挥作用。在多种心血管疾病发生、发展过程中,由于ETB受体调节异常,这种保护作用被减弱甚至逆转。本文对ETB受体的分布、信号途径、调节方式的研究进展予以综述。     

In vitro and in vivo effects of endothelin-1 and YM598, a selective endothelin ET A receptor antagonist, on the lower urinary tract

We investigated the contractile response of the lower urinary tract to endothelin-1 in vitro (rabbits) and in vivo (dogs). We also assessed the effects of a selective endothelin ET_A receptor antagonist, (E)-N-[6-methoxy-5-(2-methoxyphenoxy)[2, 2′-bipyrimidin]-4-yl]-2-phenylethenesulfonamide monopotassium salt (YM598), on endothelin-1-induced contractile responses. In the in vitro study, endothelin-1 induced contractile responses in isolated rabbit bladder base, urethra, and prostate tissues. YM598 (10^− 7–10^− 5 M) antagonized these endothelin-1-induced contractile responses without affecting the maximal responses. In the in vivo study, endothelin-1 induced the elevation of non-prostatic urethral pressure as well as prostatic urethral pressure even in the presence of tamsulosin (10 μg/kg, i.v.) in anesthetized male dogs. YM598 (0.1–3 mg/kg, i.v.) inhibited these endothelin-1-induced contractile responses in a dose-dependent fashion. These results suggest that endothelin ET_A receptors play an important role in the lower urinary tract contraction, and that the selective endothelin ET_A receptor antagonist YM598 has ameliorating effects on various urinary dysfunctions, including benign prostatic hyperplasia.     

Role of IL-18 in overt pain-like behaviour in mice

There are evidences that targeting IL-18 might be beneficial to inhibit inflammatory symptoms, including hypernociception (decrease in nociceptive threshold). The mechanism of IL-18 mechanical hypernociception depends on endothelin in rats and mice. However, the role of IL-18 in overt pain-like behaviour remains undetermined. Therefore, we addressed the role of IL-18 in writhing response induced by intraperitoneal (i.p.) injection of phenyl-p-benzoquinone (PBQ) and acetic acid in mice. Firstly, it was detected that PBQ and acetic acid i.p. injection induced a dose-dependent number of writhes in Balb/c mice. Subsequently, it was observed that the PBQ - but not the acetic acid-induced writhes were diminished in IL-18 deficient ((-/-)) mice. Therefore, considering that IFN-gamma, endothelin and prostanoids mediate IL-18-induced mechanical hypernociception, we also investigated the role of these mediators in the same model of writhing response in which IL-18 participates. It was noticed that PBQ-induced writhes were diminished in IFN-gamma(-/-) mice and by the treatment with bosentan (mixed endothelin ETA/ETB receptor antagonist), BQ 123 (cyclo[DTrp-DAsp-Pro-DVal-Leu], selective endothelin ETA receptor antagonist), BQ 788 (N-cys-2,6 dimethylpiperidinocarbonyl-l-methylleucyl-d-1-methoxycarboyl-d-norleucine, selective endothelin ETB receptor antagonist) or indomethacin (cycloxigenase inhibitor). Thus, IL-18, IFN-gamma, endothelin acting on endothelin ETA and ETB receptors, and prostanoids mediate PBQ-induced writhing response in mice. To conclude, these results further advance the understanding of the physiopathology of overt pain-like behaviour, and suggest for the first time a role for IL-18 in writhing response in mice.     

Examination of mRNA expression in rat hearts and lungs for analysis of effects of exposure to concentrated ambient particles on cardiovascular function

Epidemiological studies have suggested that fine particulate matter (f-PM) is associated with adverse effects on cardiovascular health. However, these effects on the cardiovascular system have not yet been fully elucidated. Using mRNA expression and correlation analyses, we designed the present study to elucidate (1) translocation of chemicals in inhaled f-PM to the heart, (2) induction of oxidative stress, one of the causes of cardiovascular diseases (CVDs), (3) mRNA expression related to CVDs, and (4) correlations among mRNA expression of various molecules and cardiovascular function. Wistar Kyoto male rats were exposed to concentrated ambient particles (CAPs, 0.6-1.5mg/m3) in Yokohama for 4 days (4.5h/day) or to filtered air for 3 days and CAPs for 1 day or to filtered air for 4 days. Messenger RNA expression and cardiovascular function were measured after the 4-day exposure. In samples of heart tissue, the mRNAs of cytochrome P450 (CYP) 1B1, a biomarker of exposure to chemicals; heme oxygenase-1 (HO-1), a marker of oxidative stress; and endothelin A (ET A) receptor, a receptor of vasoconstrictors, were up-regulated by CAPs; their levels were significantly correlated with the cumulative weight of CAPs in the exposure chamber. The up-regulation of ET A receptor mRNA was significantly correlated with the increase in HO-1 mRNA and weakly with the increase in mean blood pressure (Delta MBP). These results suggest the possibility that chemicals in CAPs might be translocated to the heart, where they induce oxidative stress and activate endothelin signaling, resulting in an increase in the blood pressure. The exposure to f-PM might thus affect cardiovascular function through activation of endothelin signaling.     

Antibodies against Angiotensin II Type 1 and Endothelin A Receptors: Relevance and pathogenicity

Antibodies against two G-protein coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin A receptor (ETAR) are among a growing number of autoantibodies that are found to be associated with allograft dysfunction. AT1R antibodies (AT1Rabs) and ETAR antibodies (ETARabs) have been shown to activate their target receptors and affect signaling pathways. Multiple single center reports have shown an association between presence of these antibodies and acute or chronic rejection and graft loss in kidney, heart, liver, lung and composite tissue transplantations. However, the characteristics of patients that are most likely to develop adverse outcomes, the phenotypes associated with graft damage solely due to these antibodies, and the antibody titer required to cause dysfunction are areas that remain controversial. This review compiles existing knowledge on the effect of antibodies against GPCRs in other diseases in order to bridge the gap in knowledge within transplantation biology. Future areas for research are highlighted and include the need for functional assays and treatment protocols for transplant patients who present with AT1Rabs and ETARabs. Understanding how antibodies that activate GPCRs influence transplantation outcome will have direct clinical implications for preemptive evaluation of transplant candidates as well as the post-transplant care of organ recipients.     

Coingestion of cyclooxygenase inhibitors can worsen severe paracetamol poisoning by middle-sized and small arteries vasoconstriction

Objective We report fatal cases of multifocal ischemic injuries occurring in patients awaiting liver transplantation after severe concomitant paracetamol and cyclooygenase inhibitors self-poisoning.Design and setting Case report in an intensive care unit.Patients In addition to signs of acute liver failure with a systemic inflammatory response syndrome, these three previously healthy young women demonstrated cutaneous vasoconstriction. One patient displayed a sudden ST-segment elevation with ventricular fibrillation.Interventions Angiography, plasma endothelin concentrations measurements, and autopsy.Results Radiography showed diffuse vasospasm on mesenteric and renal arteries, transiently reversed by vasodilators. We measured tenfold higher plasma endothelin concentrations than in healthy controls. Autopsy revealed no atherosis (including coronary arteries); organs showed multifocal ischemic injuries without thrombosis.Conclusions Such injuries subsequent to dramatic vasoconstriction suggest that cyclooygenase inhibition has specific deleterious vascular side effects once systemic inflammatory response syndrome is in progress during paracetamol poisoning.     

内皮素D-二聚体在婴幼儿肺炎并发心力衰竭进展中的作用及意义

目的研究婴幼儿肺炎并发不同程度心力衰竭时内皮素(ET)、D-二聚体(D-dimer)等变化及其内在联系,探讨该阶段血管内皮功能、凝血、纤溶功能的变化。方法选择肺炎及肺炎并发不同程度心力衰竭患儿80例作为试验组,健康婴幼儿20例作为对照组,均抽血检测ET、D-dimer值。结果各组间ET、D-dimer差异有统计学意义;心衰程度越重,ET、D-dimer越高,其中以肺炎并发重度心衰组明显,ET与D-dimer间呈正相关(r=0.42,P<0.01)。结论婴幼儿肺炎并发心力衰竭时存在内皮细胞功能紊乱和凝血、纤溶系统的激活。