雷公藤甲素对小鼠实验性结肠炎Th17／Treg的调节作用

目的探讨雷公藤甲素对三硝基苯磺酸（TNBS）诱导的结肠炎小鼠肠道Th17／Treg平衡的调节作用。方法40只BALB／c小鼠随机分为4组：对照组、模型组、雷公藤甲素低剂量组和高剂量组。模型组、雷公藤甲素低剂量组和高剂量组用TNBS诱导小鼠结肠炎模型,造模后,雷公藤甲素低剂量组和高剂量组分别腹腔注射35肛g·kg^-1·d^-1、70μg·kg^-1·d。雷公藤甲素,模型组每天腹腔注射生理盐水。对照组用50％乙醇溶液灌肠后每天腹腔注射生理盐水。2周后处死各组小鼠,评估各组小鼠结肠组织的大体和组织学评分,实时荧光定量RT-PCR检测结肠组织IL-17、RORC和Foxp3mRNA表达水平。结果雷公藤甲素低剂量和高剂量组小鼠结肠组织大体和组织学评分显著低于模型组（P〈0．05）,结肠组织IL-17、RORCmRNA表达显著低于模型组（P〈0．05）,Foxp3mRNA表达显著高于模型组（P〈0．05）,雷公藤甲素低剂量、高剂量组与对照组比较,差异无统计学意义（P〉0．05）。结论雷公藤甲素可能通过下调RORC表达抑制Th17细胞分化、IL-17产生,上调Foxp3促进Treg细胞形成,从而调节结肠炎小鼠Th17／Treg平衡,抑制肠道炎症。     

牛磺酸对三硝基苯磺酸诱导的结肠炎大鼠肠纤维化的抑制作用

目的 探讨牛磺酸对三硝基苯磺酸(TNBS)诱导的结肠炎大鼠肠纤维化的影响.方法 32只SD大鼠均分为对照组、模型组、低剂量和高剂量牛磺酸组.对照组以0.9%氯化钠溶液灌肠,其余3组以TNBS灌肠诱导建立结肠炎模型.低剂量和高剂量牛磺酸组于造模前1周每日分别给予牛磺酸400和800 mg/kg干预,直至造模结束.观察大鼠临床表现及疾病活动指数(DAI),行结肠大体评分和组织学评分,检测大鼠结肠长度、结肠重量.测定结肠组织中羟脯氨酸(Hyp)、Ⅰ型胶原蛋白、转化生长因子-β1(TGF-β1)蛋白和mRNA、Smad3蛋白和mRNA水平.结果 与对照组相比,模型组大鼠体重减轻、DAI评分升高、结肠狭窄伴近端扩张、结肠长度缩短、结肠重量增加、大体评分也显著升高(P<0.01).牛磺酸干预后,大鼠体重、DAI评分、结肠长度等指标均有所改善.模型组纤维化评分为1.88±0.35.较对照组明显增加(0.25±0.46,P<0.01);低剂量和高剂量牛磺酸组纤维化评分分别为1.25±0.71和0.75±0.47,较模型组下降(P<0.05).模型组大鼠结肠Hyp、TGF-β1、Ⅰ型胶原蛋白、Smad3蛋白和mRNA含量均较低剂量和高剂量牛磺酸组明显上升(P值均<0.05).结论 牛磺酸能有效抑制TNBS诱导的结肠炎大鼠肠纤维化,其抗纤维化机制可能与下调TGF-β1、抑制TGF-β/Smad3通路有关,为解决克罗恩病肠纤维化和肠狭窄提供一定的实验依据.     

姜黄素通过过氧化物酶体增生物激活受体-γ在大鼠实验性结肠炎中发挥抗炎作用

背景：研究显示姜黄素可激活过氧化物酶体增生物激活受体（PPAR）-γ，抑制三硝基苯磺酸（TNBS）诱导的大鼠结肠炎症。目的：以姜黄素和PPAR-γ拮抗剂GW9662单独或联合干预结肠炎模型大鼠，探讨姜黄素在大鼠实验性结肠炎中的抗炎机制。方法：以直肠内注入TNBS／乙醇溶液制备大鼠结肠炎模型。模型大鼠分别腹腔注射二甲基亚砜（DMSO）、姜黄素、GW9662或GW9662＋姜黄素2周，评价各组大鼠的死亡率、结肠损伤评分、血清促炎因子白细胞介素（IL）-2和抗炎因子IL-10水平以及结肠组织PPAR-γ和核因子（NF）-κB的表达。结果：与模型对照组相比，姜黄素能明显降低大鼠死亡率、结肠黏膜大体、组织学损伤评分和血清IL-2水平，升高血清IL-10水平，结肠组织PPAR-γ表达增高，NF-κB表达减低（P〈0．05）；GW9662＋姜黄素组大鼠结肠炎症无明显改善。正常对照组、模型对照组和姜黄素组PPAR-γ与NF-κB的表达均呈负相关（P〈0．01）。结论：姜黄素可通过PPAR-γ途径负性调节NF-κB的表达，在TNBS诱导的大鼠结肠炎中发挥抗炎作用。     

辛伐他汀对大鼠结肠炎结肠纤维化的初步研究

目的 探讨辛伐他汀对2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠结肠炎结肠纤维化的作用及机制.方法 48只雄性SD大鼠均分为6组,分别为健康对照组、TNBS组、辛伐他汀治疗Ⅰ组和治疗Ⅱ组(造模后0～21 d,分别用辛伐他汀5mg/kg和20 mg/kg治疗)、治疗Ⅲ组和治疗Ⅳ组(造模后7～21 d,分别用辛伐他汀5mg/kg和20mg/kg治疗).观察大鼠体质量变化及疾病活动指数(DAI),对大鼠结肠行大体评分、组织学损伤及纤维化评分.RT-PCR检测Ⅰ型胶原和结缔组织生长因子(CTGF) mRNA水平.Western印迹法检测Ⅰ型胶原、CTGF和磷酸化肌球蛋白磷酸酶目标亚单位-1(p-MYPT-1)蛋白的表达.组间比较采用单因素方差分析.结果 与对照组相比,TNBS组大鼠结肠长度缩短,结肠质量增加,DAI评分、大体评分、组织学损伤及纤维化评分均显著升高,结肠组织中Ⅰ型胶原的表达水平也明显升高.辛伐他汀干预后,大鼠结肠长度和质量均有改善,DAI评分、大体评分、组织学损伤及纤维化评分、结肠组织中Ⅰ型胶原及CTGF的表达均比TNBS组降低,p-MYPT-1的表达在治疗Ⅰ组为0.68±0.22,治疗Ⅱ组为0.59±0.27,治疗Ⅲ组为0.71±0.20,治疗Ⅳ组为0.59±0.25,均低于TNBS组的0.97±0.30(F-5.169,P＜0.05).4个治疗组之间差异无统计学意义(P＞0.05).结论 辛伐他汀能有效防治TNBS诱导的大鼠结肠炎结肠纤维化,机制可能与抑制Rho激酶活化、下调CTGF过表达有关.     

复方黄柏液对大鼠TNBS结肠炎的治疗机制探讨

背景：临床上采用复方黄柏液保留灌肠辅助治疗溃疡性结肠炎（UC）疗效满意,但其作用机制尚不清楚。目的：探讨复方黄柏液对三硝基苯磺酸（TNBS）诱发的大鼠结肠炎模型炎症损伤的治疗作用及其可能机制。方法：40只成年雌性Sprague-Dawley大鼠随机分成四组,正常对照组不予处理,其余三组以TNBS／乙醇溶液灌肠制作结肠炎模型后．分别予0．9％NaCl溶液1ml、5-氨基水杨酸（5-ASA）200mg／kg和复方黄柏液1ml灌肠,连续14d。治疗后评估大鼠疾病活动指数（DAI）以及结肠大体、组织学损伤情况;检测结肠组织髓过氧化物酶（MPO）活性和白三烯B4（LTB4）含量;心脏采血,流式细胞术检测中性粒细胞凋亡率。结果：与正常对照组相比,TNBS模型组DAI、结肠大体和组织学评分、结肠组织MPO活性和LTB。含量均显著升高,血中性粒细胞凋亡率显著降低（P〈0．01）;5-ASA治疗组和复方黄柏液治疗组上述指标均较TNBS模型组显著改善（P〈0．01）,两组间差异则无统计学意义。结论：复方黄柏液灌肠对大鼠TNBS结肠炎具有明显治疗作用,促进中性粒细胞凋亡、清除结肠局部损伤因子（MPO、LTB。）可能为其作用机制之一。     

奥曲肽对溃疡性结肠炎大鼠肠组织NF-κB p65的影响

目的探讨生长抑素（SST）类似物—奥曲肽对溃疡性结肠炎（UC）大鼠结肠组织核因子-κB（NF-κB）p65蛋白活性的影响及其机制。方法将雌性SD大鼠随机分为正常对照组、奥曲肽对照组、模型组、治疗组,每组各7只。模型组、治疗组大鼠用三硝基苯磺酸（TNBS）/乙醇溶液灌肠复制UC模型。评价各组实验大鼠大体及组织病理学改变,采用Western blot法检测结肠NF-κB p65蛋白的表达。结果奥曲肽可以显著改善结肠组织大体和组织学评分,降低NF-κB p65表达。结论NF-κB与UC发病关系密切,奥曲肽可能通过影响炎症反应的信号通路达到治疗目的。     

大黄素对TNBS诱导大鼠肠纤维化的影响

目的:观察大黄素对结肠炎大鼠模型肠纤维化的影响,探讨其抗纤维化作用机制.方法:以三硝基苯磺酸(trinitrobenzene sulphonic acid,TNBS)诱导的结肠炎大鼠为纤维化模型,将34只SD大鼠分成正常对照组、模型组和大黄素组,模型组和大黄素组予以TNBS诱导肠纤维化,大黄素组每日给予大黄素40mg/kg灌胃,其余组则给予等体积盐溶液.实验过程中观察小鼠体质量、大便性状和活动变化,给予DAI评分,实验结束后收集结肠组织标本,给予大体和组织学评分,并采用HE染色及Masson胶原三色染色观察大鼠结肠组织损伤和纤维化程度,采用荧光定量PCR法检测结肠黏膜中TGF-1、胶原Ⅰ、胶原Ⅲ、Smad3、-SMA和E-cad mRNA表达.结果:与模型组相比,大黄素组一般情况、结肠组织大体和组织学评分及纤维化程度均出现明显改善.大黄素组TGF-β1、胶原Ⅰ、胶原Ⅲ、Smad3和-SMA mRNA表达较模型组明显降低(1.27±0.78vs4.56±3.14;0.60±0.59vs2.15±1.22;0.92±1.38vs3.34±1.47;3.11±2.81vs8.77±6.40;0.87±0.62vs2.40±1.15,均P<0.05),而E-cad mRNA表达明显升高(1.01±0.34vs0.30±0.23,P<0.05).结论:大黄素对TNBS诱导的大鼠肠纤维化模型具有一定的抗纤维化作用,该作用可能与其下调TGF-1/Smad信号通路抑制EMT发生有关.     

IL-17、IL-23、IL-6、TGF-β1和Foxp3在实验性结肠炎中的表达

目的 观察2、4、6-三硝基苯磺酸(TNBS)诱导的大鼠结肠炎模型中结肠Foxp3、TGF-β1的表达及外周血清IL-17、IL-23和IL-6的表达,以探讨Th17细胞在IBD的作用.方法 10只SD大鼠以三硝基苯磺酸(TNBS)/L醇溶液灌肠诱导结肠炎模型.另取10只大鼠作为正常对照组(0.9%NaCl溶液灌肠).干预2周后行结肠大体损伤指数(CMDI)和组织学损伤指数(TDI)评分,以酶联免疫吸附测定(ELISA)检测血清白介素-6(Interteukin 6,IL-6)、IL-17和IL-23水平,以免疫组化方法(SP法)检测结肠组织转化生长因子-β1(TGF-β1)和叉头样转录因子-3(Foxp3)表达.结果 与正常组相比,结肠炎模型组CMDI和TDI显著升高(P<0.01),血清IL-6、IL-17和IL-23水平明显升高(P<0.05),结肠组织TGF-β1和Foxp3明显降低(P<0.05).结论 在TNBS诱导的大鼠实验性结肠炎中,IL-6可能通过介导T细胞向Th17或Treg细胞的分化,促进或抑制肠道炎症.     

丁酸钠对TNBS结肠炎模型大鼠肠黏膜修复的影响

背景：肠道黏膜的炎症损伤和修复是炎症性肠病（IBD）的重要特征之-。丁酸盐为肠上皮细胞的主要能量来源,参与了肠道黏膜内稳态的维持并具有抗炎效应。目的：观察丁酸钠对结肠炎模型大鼠肠黏膜炎症损伤和修复的影响．探讨其治疗IBD的可能机制。方法：以三硝基苯磺酸（TNBS）诱导大鼠结肠炎模型并予丁酸钠或美沙拉嗪治疗,同时设置正常对照组和结肠炎模型组。于急、慢性炎症期分批处死大鼠,行结肠组织学检查和评分,免疫组化方法检测结肠组织中与黏膜修复相关的转化生长因子-β1（TGF-β1）、血管内皮生长因子（VEGF）表达,ELISA方法检测血浆促炎细胞因子白细胞介素．8（IL-8）、抗炎细胞因子IL-10水平。结果：与结肠炎模型组相比,丁酸钠治疗组一般情况和结肠组织学表现有所改善．美沙拉嗪治疗组则有明显改善。丁酸钠治疗组和美沙拉嗪治疗组结肠组织TGF—β1阳性表达率显著高于结肠炎模型组（P〈0．05）,VEGF阳性表达率无明显变化．慢性炎症期血浆IL_8水平显著降低（P〈0．05）．IL-10水平显著增高（P〈0．05）。结论：丁酸钠对TNBS结肠炎模型大鼠的肠黏膜修复有-定促进作用,该作用可能与其增加TGF-β1表达和调节促炎细胞因子与抗炎细胞因子平衡有关。     

白芍总苷对TNBS诱导的大鼠实验性结肠炎的影响

背景：白芍总苷（TGP）具有抗炎、免疫调节等作用,其对炎症性肠病是否具有治疗作用尚不清楚。目的：探讨TGP对大鼠实验性结肠炎的影响及其可能机制。方法：50只大鼠以三硝基苯磺酸（TNBS）／乙醇溶液灌肠诱导结肠炎模型,分为结肠炎模型组、低、中、高剂量TGP组（25、50、100mg／kgTGP）和阳性药物对照组（100mg／kg奥沙拉秦）。10只大鼠作为正常对照组（0．9％NaCl溶液灌肠）。实验期间评估各组疾病活动指数（DAI）;干预2周后行结肠大体损伤指数（CMDI）和组织学损伤指数（TDI）评分,以酶联免疫吸附测定（ELISA）检测血清肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-1O）水平,以免疫组化方法检测结肠组织磷酸化p38丝裂原活化蛋白激酶（p—p38MAPK）表达。结果：与结肠炎模型组相比,高剂量TGP组实验期间DAI均值显著降低（P＜0．01）;中、高剂量TGP组CMDI和TDI显著降低,血清TNF-α水平降低,IL-10水平升高,结肠组织p-p38MAPK表达降低（P＜0．05）。高剂量TGP的疗效与奥沙拉秦无明显差异。结论：TGP可能通过抑制p38MAPK激活,抑制TNF-α分泌,促进IL—10分泌,改善免疫调节紊乱,从而减轻TNBS诱导的大鼠实验性结肠炎的症状和结肠炎性损伤。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.