辛伐他汀对C-反应蛋白诱导的抵抗素表达的实验研究

目的:探讨辛伐他汀对C-反应蛋白CRP诱导的人外周血单核细胞抵抗素mRNA和蛋白表达的影响。方法:分离培养人外周血单核细胞,分别与不同浓度的辛伐他汀(0.1,1,10μmmol/L)预孵育2 h,再与25μg/mL CRP共同培养24 h,分别用实时定量PCR和ELISA方法检测单核细胞抵抗素mRNA表达及细胞培养液中抵抗素的浓度。结果:辛伐他汀呈剂量依赖性地抑制CRP诱导的抵抗素mRNA和蛋白表达。结论:辛伐他汀可显著抑制CRP诱导的抵抗素的表达,提示CRP和抵抗素可能参与动脉粥样硬化(As)的进展,他汀类药物可能通过调节CRP诱导的抵抗素过度表达发挥其抗As作用。     

C反应蛋白和肿瘤坏死因子-α对单核细胞妊娠相关血浆蛋白-A mRNA表达影响的实验研究

目的 研究C反应蛋白(CRP)和肿瘤坏死因子-α(TNF-α)对人外周血单核细胞妊娠相关血浆蛋白-A(PAPP-A) mRNA表达的影响.方法 采用密度梯度离心法分离人外周血单核细胞,用RT-PCR方法分别观察CRP和TNF-α刺激单核细胞PAPP-A mRNA表达的时间及剂量效应.结果 与空白对照组PAPP-A的mRNA表达(0.1842±0.0101)相比,CRP(20 mg/L)刺激单核细胞2 h后,PAPP-A mRNA表达开始显著增加(0.2128±0.0136),于24 h达最高值(0.6837±0.1360),呈时间依赖性.rhTNF-α(100 ng/ml)刺激后,PAPP-A mRNA表达在2 h迅速升高并达峰值(1.2546±0.0866),24 h仍高于空白对照组(0.8203±0.0413).CRP和rhTNF-α均可呈剂量依赖性诱导PAPP-A的mRNA表达,其中CRP(1、5、10和20 mg/L)刺激组PAPP-A 的mRNA表达分别为0.2544±0.0611、0.4177±0.1200、0.5828±0.0152和0.6837±0.1360,rhTNF-α(5、10、25、50和100 ng/ml)刺激组分别为0.2424±0.1378、0.3335±0.0196、0.5742±0.0131、0.6913±0.0219和0.8203±0.0413.放线菌素D(1 μg/ml)能抑制CRP和rhTNF-α对单核细胞PAPP-A mRNA表达的诱导作用.结论 促炎因子CRP和rhTNF-α可在转录水平直接调控人外周血单核细胞PAPP-A的基因表达,这可能是急性冠状动脉综合征患者循环中PAPP-A水平升高的机制之一.     

普伐他汀抑制C-反应蛋白诱导的人外周血单核细胞白细胞介素-6 mRNA表达

目的观察普伐他汀对急性冠状动脉综合征(ACS)患者外周血单核细胞(PBMC)在一定浓度的C-反应蛋白(CRP)诱导下IL-6基因表达与分泌的影响.方法体外培养3组人群[ACS组(15例)、稳定型心绞痛组(SAP组,13例)与对照组(15例)]的PBMC,CRP(20μg/ml)刺激24 h.普伐他汀以不同浓度(0.1×10-6,1×10-6,5×10-6 ,10×10-6mol/L)预先孵育ACS组PBMC 2 h后继以CRP刺激24 h.酶联免疫吸附试验(ELISA)分析培养液上清中的IL-6水平,RT-PCR分析细胞IL-6 mRNA表达水平.结果20μg/ml CRP刺激状态下3组的IL-6分泌均较其基础状态显著增加(P<0.05),CRP明显增加PBMC IL-6的分泌;ACS组PBMC受CRP刺激后IL-6表达水平为(3129.5±333.4 )ng/L,较对照组(987.3±102.3)ng/L和SA组(990.9±134.8) ng/L明显增高(P<0.05).普伐他汀以剂量依赖方式下调ACS组PBMC IL-6mRNA表达和IL-6分泌.结论CRP明显增强ACS组PBMC IL-6mRNA表达和IL-6分泌.一定浓度的CRP能诱导血单核细胞IL-6表达增加,在ACS患者中更为明显,普伐他汀有效降低CRP对ACS患者单核细胞的致炎症效应.     

C反应蛋白对单核细胞妊娠相关血浆蛋白A表达的影响及机制研究

目的探讨C反应蛋白(CRP)对单核细胞妊娠相关血浆蛋白A(PAPP-A)蛋白和基因表达的影响及其机制。方法采用密度梯度离心法分离人外周血单核细胞,分别采用Western blot和实时荧光定量聚合酶链反应方法观察CRP刺激单核细胞PAPP-A蛋白和mRNA表达的时间及剂量效应。采用Active Motif的专利技术测定CRP对单核细胞核转录因子κB(NF-κB)活性的影响。同时观察给予NF-κB抑制剂BAY11-7082预处理后,CRP对单核细胞PAPP-A表达的影响。结果 CRP(20 mg/L)刺激单核细胞2 h后,PAPP-A的蛋白和mRNA表达开始增加,呈时间依赖性,同时呈剂量依赖性诱导单核细胞的PAPP-A表达。CRP可显著增加单核细胞NF-κB p65水平,在给予NF-κB抑制剂BAY11-7082预处理后,CRP诱导PAPP-A表达的作用受到抑制。结论 CRP可通过激活NF-κB上调单核细胞PAPP-A的蛋白和基因表达,这可能是急性冠状动脉综合征患者循环中PAPP-A升高的机制之一。     

辛伐他汀抑制人外周血单核巨噬细胞脂蛋白相关磷脂酶A2表达

目的 观察辛伐他汀对人外周血单核巨噬细胞脂蛋白相关磷脂酶A2(Lp-PLA2)表达的影响,并探讨其调控机制.方法 分离培养人外周血单核巨噬细胞,实验分为脂多糖(LPS)组、辛伐他汀组和丝裂原活化蛋白激酶(MAPK)干预组.LPS组:分别用不同浓度(0、1、10、102、103和104ng/ml)的LPS与细胞共同孵育6 h,观察不同浓度的辛伐他汀对LPS诱导的Lp-PLA2 mRNA和蛋白表达的影响;并用1μg/ml的LPS与细胞孵育不同时间(0、6、12、24和48 h),观察辛伐他汀作用不同时间对LPS诱导的Lp-PLA2 mRNA和蛋白表达的影响.辛伐他汀组:1 μg/ml的LPS+不同浓度的辛伐他汀(10-2～10-7mmol/L)与单核巨噬细胞共同孵育24 h,1 μg/ml LPS+10-3mmol/L的辛伐他汀与单核巨噬细胞孵育不同时间(0、6、24、24和48 h),观察辛伐他汀对LPS诱导的Lp-PLA2mRNA和蛋白表达及酶活性的影响.MAPK组:分别用10 μmol/L的p38抑制剂SB203580、20 μmol/L的ERK抑制剂U0126和20 μmol/L的JNK抑制剂SP600125预处理30 min后,将单核巨噬细胞与1μg/ml的LPS共同孵育24 h,观察MAPK信号通路在LPS介导的Lp-PLA2表达中的作用.逆转录-多聚酶链反应(RT-PCR)方法 检测Lp-PLA2 mRNA表达,比色法测定酶活性,Western blot方法 检测Lp-PLA2蛋白表达以及p38-MAPK蛋白及磷酸化水平.结果 (1)0.1μg/ml的LPS刺激6 h即可显著增加单核巨噬细胞Lp-PLA2 mRNA和蛋白的表达及其酶活性,并且随LPS浓度的增加和刺激时间的延长,该作用增强.(2)辛伐他汀可以明显抑制LPS诱导的Lp-PLA2的表达增加,并且降低酶活性,该作用呈浓度及时间依赖性.(3)辛伐他汀抑制LPS诱导的p38MAPK蛋白活化,p38MAPK的抑制剂SB203580可以完全阻断LPS介导的Lp-PLA2蛋白表达增加,与辛伐他汀作用相似.而MEK1/2的抑制剂U0126和JNK的抑制剂SP600125对LPS介导的Lp-PLA2蛋白表达的增加没有影响.结论 在培养的人外周血单核巨噬细胞中,辛伐他汀可以明显抑制LPS诱导的Lp-PLA2 mRNA和蛋白表达,降低Lp-PLA2酶活性,该作用至少部分由抑制p38MAPK信号转导通路介导.     

CRP和LPS致单核细胞NF-κB活化及IL-6合成的比较

目的观察C-反应蛋白和脂多糖诱导人外周血单核细胞合成白细胞介素-6水平及两者致单核细胞NF-κB活化的程度，比较其致炎作用。方法Ficoll密度梯度离心法分离人外周血单核细胞，应用ELISA法观察CRP和LPS刺激单核细胞产生IL-6的时间效应，比较其峰值。免疫细胞化学观察两者致单核细胞NF-κB活化的程度。结果CRP和LPS刺激IL-6合成开始的时间分别是4小时和2小时，呈时间依赖性，在24小时达高峰。LPS组峰值高于CRP组。在刺激16小时后，LPS组NF-κB活化的程度高于CRP组。结论CRP和LPS均能活化NF-κB，并诱导单核细胞产生IL-6；10ng／ml LPS的致炎作用强于20ug／ml CRP。     

肿瘤坏死因子-α对单核细胞妊娠相关血浆蛋白A表达的影响及调节机制

目的探讨肿瘤坏死因子-α(TNF-α)对人外周血单核细胞妊娠相关血浆蛋白(PAPP)-A蛋白和mRNA表达的影响及其机制。方法采用密度梯度离心法分离及培养人外周血单核细胞,采用Western印迹法和实时荧光定量PCR法观察TNF-α诱导单核细胞PAPP-A蛋白和mRNA表达的时间及剂量效应。采用TransAMTM技术检测TNF-α对单核细胞NF-κB活性的影响。此外观察给予核转录因子κB(NF-κB)抑制剂BAY11-70682预处理后,TNF-α对单核细胞PAPP-A表达的影响。结果 TNF-α(100 ng/ml)刺激单核细胞后,PAPP-A的蛋白和mRNA表达分别在8 h和2 h达高峰,且呈剂量依赖性诱导单核细胞的PAPP-A表达。TNF-α可显著增加单核细胞的磷酸化NF-κB p65水平,在给与BAY11-70682预处理后,TNF-α诱导PAPP-A表达的作用受到抑制。结论促炎因子TNF-α通过激活NF-κB途径上调单核细胞PAPP-A的蛋白和基因表达,这可能是急性冠脉综合征(ACS)患者血清PAPP-A升高的机制之一。     

辛伐他汀对C反应蛋白诱导的单核细胞白细胞介素-6合成的影响

目的　探讨辛伐他汀对C反应蛋白 (C reactiveprotein ,CRP)诱导的人外周血单核细胞白细胞介素 6 (interleu kin 6 ,IL 6 )合成的影响 ,观察辛伐他汀的抗炎作用。方法　密度梯度离心法分离人外周血单核细胞 ,应用酶联免疫吸附测定法观察CRP刺激单核细胞产生IL 6的时间 剂量效应 ,其峰值与辛伐他汀抑制剂组比较。结果　CRP刺激IL 6合成开始的时间是 4h ,呈时间依赖性和剂量依赖性 ,在 2 4h达高峰。辛伐他汀 (10 - 8～ 10 - 6 mol L)呈剂量依赖性抑制单核细胞IL 6合成。结论　辛伐他汀能抑制CRP诱导的单核细胞IL 6合成 ;辛伐他汀对炎症反应的抑制作用提示该药物可用于预防和治疗冠心病。     

载脂蛋白A1对胆固醇逆转运及三磷酸腺苷结合盒转运体A1表达的影响

目的 观察载脂蛋白A1(apoAl)对人急性单核细胞白血病细胞株(THP-1)源性泡沫细胞内胆固醇、胆固醇酯含量和三磷酸腺苷结合盒转运蛋白A1(ABCAl)表达的影响和机制.方法 以50 ng/ml的佛波酯诱导人THP-1,使其分化为巨噬细胞,再经50μg/ml氧化型低密度脂蛋白充分诱导使其转变为负脂的泡沫细胞;然后用不同浓度apoAl(5μg/ml、10μg/ml、15μg/ml、20 μg/ml)孵育泡沫细胞24 h,以apoAl(10μg/ml)孵育泡沫细胞6 h、12 h、24 h.采用油红O染色观察细胞内脂滴的变化,用氧化酶法检测细胞内总胆固醇、游离胆固醇和胆固醇酯的含量;用反转录聚合酶链反应检测不同浓度apoAl干预泡沫细胞后ABCA1 mRNA的表达;用免疫荧光法检测经不同浓度和不同时间apoAl和ABCAl多克隆抗体干预泡沫细胞后ABCA1蛋白的表达.结果 (1)THP-1经佛波酯(50 ng/ml)和氧化型低密度脂蛋白(50μg/ml)分别干预48 h后可成功诱导为富含脂质的泡沫细胞;(2)apoA1可促进THP-1巨噬细胞源性泡沫细胞内胆固醇逆向转运,减少细胞内胆固醇含量,呈浓度依赖性和时间依赖性;(3)随着apoA1干预浓度增加,THP-1巨噬细胞源性泡沫细胞内ABCA1 mRNA的表达变化不显著,但蛋白表达增加,0 μg/ml与5 μg/ml、10μg/ml、15μg/ml、20μg/ml apoAl干预浓度下油红O染色阳性细胞率分别为(55±4)%与(43±9)%、(33±4)%、(28±1)%、(26±2)%,差异有统计学意义(均P<0.05);(4)ABCAl抗体干预可增加THP-1巨噬细胞源性泡沫细胞ABCA1蛋白的表达.结论 apoA1-ABCA1通路参与泡沫细胞胆固醇逆向转运,apoA1起关键作用,apoA1增加ABCA1蛋白的表达可能与降低ABCA1蛋白的降解有关.     

缬沙坦对不同浓度C-反应蛋白诱导的单核细胞白细胞介素-6合成的影响

目的通过研究缬沙坦对C-反应蛋白(CRP)诱导的正常人外周血单核细胞合成白细胞介素-6(IL-6)的影响,观察缬沙坦的抗炎作用。方法采用密度梯度离心法分离人外周血单核细胞,应用酶联免疫吸附试验分别观察CRP(15、、10及20 mg/L)刺激单核细胞产生IL-6的时间及剂量效应,其峰值与缬沙坦抑制剂进行比较。结果CRP刺激单核细胞IL-6合成呈时间依赖性和剂量依赖性,20 mg/L CRP与5 mg/L CRP诱导IL-6合成开始的时间是4 h,在24 h达高峰,其峰值分别是(904±77)ng/L和(698±52)ng/L。高浓度缬沙坦(≥10-3mol/L)能抑制20 mg/LCRP诱导的单核细胞IL-6合成,较低浓度缬沙坦(1×10-6mol/L~1×10-3mol/L)能抑制5 mg/L CRP诱导的单核细胞IL-6合成。结论缬沙坦可用于轻度炎症时抗细胞因子治疗。     

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.