阿托伐他汀对糖尿病大鼠肾皮质肾上腺髓质素受体表达的影响

目的探讨肾上腺髓质素受体(ADMR)在糖尿病(DM)大鼠肾脏病变时的变化及阿托伐他汀对ADMR表达的影响。方法将SD大鼠分为3组:正常对照组、DM对照组和阿托伐他汀干预组。采用腹腔注射链脲佐菌素(STZ)制备DM动物模型,阿托伐他汀15mg·kg-1·d-1灌胃。通过RT-PCR方法检测肾皮质中ADMR mRNA的表达,运用Western印迹方法检测肾皮质中ADMR蛋白的表达。结果(1)阿托伐他汀干预组大鼠体重、糖化血红蛋白(HbA1C)及血糖与DM组比较差异无统计学意义,24h尿白蛋白排泄率显著降低[(35.9±1.7)μg/24hvs(19.8±1.5)μg/24h,P<0.01];(2)阿托伐他汀干预组大鼠肾皮质中ADMR mRNA及蛋白的表达均显著高于DM组(均P<0.05)。结论阿托伐他汀可上调DM大鼠肾皮质中ADMR基因和蛋白的表达,ADMR可能参与了阿托伐他汀对肾脏的保护作用。     

氟伐他汀对实验性动脉粥样硬化家兔血管壁NF-κB表达的影响

目的:观察氟伐他汀对动脉粥样硬化(As)家兔模型血管壁核因子kappaB(NFκB)活性及mRNA表达的影响。方法:应用免疫组化法观察NFκB活性,应用原位杂交法观察NFκBmRNA表达。结果:氟伐他汀组与高脂饮食组相比As病变明显减轻(P<0.01),NFκB活性明显降低(P<0.01),NFκBmRNA表达明显减弱(P<0.01)。结论:氟伐他汀抗As作用机制与抑制NFκB活性有关。     

氟伐他汀对实验性动脉粥样硬化家兔血脂及动脉粥样斑块的影响

目的观察氟伐他汀对实验性动脉粥样硬化家兔血脂及动脉粥样斑块的影响情况。方法雄性新西兰白兔34只，体重2.0～2.5kg。随机分为四组(1)正常对照组(n=7)假手术+正常饲料；(2)病理对照组(n=10)动脉内膜剥脱术+高脂饲料；(3)用药5周组(n=7)动脉内膜剥脱术+高脂饲料+4周后应用氟伐他汀5周(10mg·kg(-1)·d(-1))。(4)用药9周组(n=10)动脉内膜剥脱术+高脂饲料+应用氟伐他汀9周(10mg·kg(-1)·d(-1))。观察实验各阶段各组家兔血脂及血管病理形态学变化。结果实验前各组家兔血清脂质之间均无明显差别。实验9周时，两个用药组HDL浓度均显著高于两个对照组(P＜0.05)。病理结果显示两个用药组主动脉及髂动脉动脉粥样硬化程度明显轻于病理对照组。结论氟伐他汀具有明显的降血脂及抑制动脉粥样硬化进展的作用。     

支气管哮喘豚鼠肺内肾上腺髓质素和受体表达及地塞米松的影响

肾上腺髓质素(ADM)是从肾上腺嗜铬细胞瘤中分离出的一种新的生物活性肽…，具有舒张血管、扩张支气管等多种作用^[2]。支气管哮喘(简称哮喘)发作时ADM及其受体(ADMR)基因表达过程仍未明确，我们的研究旨在观察哮喘豚鼠肺内ADM／ADMR基因的表达以及是否受糖皮质激素的调控。     

肾上腺髓质素受体及其在肾脏中的表达和调节

肾上腺髓质素(AM)是一种生物活性多肽,可以与降钙素基因相关肽受体、降钙素受体样受体和孤儿G蛋白偶联受体RDC-1、L1作用,这些受体活化后可通过激活cAMP、一氧化氮合酶等多种信号转导通路实现生理功能。近年有文献报道,肾脏疾病明显影响肾脏中AM受体——主要是受体活性修饰蛋白的表达和调节,研究其病理生理作用和机制对临床肾病的诊疗、防治及新型药物的研发具有十分重要的作用。     

氟伐他汀对内膜损伤后动脉粥样硬化家兔内皮功能的改善作用

为观察氟伐他汀对实验性动脉粥样硬化家兔内皮系统及凝血纤溶系统功能的作用 ,将 2 8只雄性新西兰白兔随机分为正常组、病理组、用药 5周组及用药 9周组 ,每组各 7只。病理组和用药组给予高脂饮食 5天后行内膜剥脱术 ,术后给高脂饮食 8周 ,正常组仅给予普通饮食及假手术。用药 9周组每天给高脂饮食同时给予氟伐他汀 (10 μg/g) ,用药 5周组每天给高脂饮食 4周后再每天加给氟伐他汀 (10 μg/g)。然后测定不同时间点家兔血浆 6-酮 -前列腺素F1α、血栓素B2 、内皮素、一氧化氮、组织型纤溶酶原激活剂、纤溶酶原激活剂抑制因子及纤维蛋白原水平。结果发现 ,实验前各组家兔血浆内皮功能指标及凝血纤溶功能指标之间均无明显差别。实验第 9周两个用药组血栓素B2 / 6 -酮 -前列腺素F1α比值、内皮素浓度及纤溶酶原激活剂抑制因子浓度均显著低于病理组 (P <0 .0 5 ) ;病理组血栓素B2 浓度明显高于正常组 (P <0 .0 5 ) ,一氧化氮及组织型纤溶酶原激活剂浓度明显低于正常组(P <0 .0 1) ;用药组 6 -酮 -前列腺素F1α浓度有高于病理组的趋势 ,纤维蛋白原浓度有低于病理组的趋势。结果提示 ,氟伐他汀具有明显的改善血管内皮功能及凝血纤溶系统功能的作用。     

瑞舒伐他汀对高脂饲养大鼠心肌脂联素及其受体表达的影响

目的　探讨瑞舒伐他汀对高脂饲养大鼠心肌脂联素及其受体mRNA和蛋白表达的影响。方法　8周龄Wistar大鼠48只,随机分为对照组、高脂饲养组、高脂饲养＋瑞舒伐他汀组,20周后,全自动生化分析仪测定血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDLC）、高密度脂蛋白胆固醇（HDLC）、血糖,ELISA测定血清脂联素,RT-qPCR和　Western　blot测定心肌组织脂联素及其受体　mRNA和蛋白的表达。结果　与对照组相比,高脂饲养组大鼠血清TG、TC、LDLC、血糖、脂联素升高（P＜0.01）,HDLC降低（P＜0.01）。与高脂饲养组相比,高脂饲养＋瑞舒伐他汀组血清TG、TC、LDLC、脂联素降低（P＜0.05）,　HDLC升高（P＜0.01）,血糖无明显差异（P＞0.05）。与对照组相比,高脂饲养组心肌脂联素mRNA和蛋白表达升高（P＜0.01）,心肌脂联素受体mRNA和蛋白表达降低（P＜0.05）。与高脂饲养组相比,高脂饲养＋瑞舒伐他汀组心肌脂联素mRNA和蛋白表达降低（P＜0.05）,心肌脂联素受体1　mRNA和蛋白表达升高（P＜0.05）,心肌脂联素受体2　mRNA和蛋白表达无明显差异（P＞0.05）。结论　高脂饲养大鼠过程中,可出现血清脂联素升高,心肌脂联素mRNA和蛋白表达上调,心肌脂联素受体mRNA和蛋白表达下调,瑞舒伐他汀可以部分逆转这些作用。     

氟伐他汀对实验性动脉粥样硬化家兔血脂及动脉粥样斑块的影响

目的：观察氟伐他汀对实验性动脉粥样硬化家兔血脂及动脉粥样块斑块的影响情况。方法：雄性新西兰白兔34只，体重2．0－2.5kg。随机分为四组：（1）正常对照组（n=7)：假手术＋正常饲料；（2）病理对照组（n=10）；动脉内膜剥脱术＋高脂饲料；（3）用药5周组（n＝7）：动脉内膜剥脱术＋高脂饲料＋4周后应用氟伐他汀5周（10mg.kg^-1.d^-1)。（4）用药9周组（n＝10）：动脉内膜剥脱术＋高脂饲料＋应用氟伐汀9周（10mg.kg^-1.d^-1）。观察实验各阶段各组家兔血脂及血管病理形态学变化。结果：实验前各组家兔血清脂质之间均无明显差别。实验9周时，两个用药组HDL浓度均显著高于两个对照组（P＜0．05）。病理结果显示两个用药组主动脉及髂动脉动脉粥样硬化程度明显轻于病理对照组。结论：氟伐他汀具有明显的降血脂及抑制动脉粥样硬化进展的作用。     

肾上腺髓质素和内皮素在糖尿病大鼠肾组织的表达

目的 探讨肾上腺髓质素(ADM)、内皮素-1(ET-1)及其受体在糖尿病肾病(DN)发病过程中的动态变化.方法 单侧肾切除大鼠腹腔注射链脲佐菌素(STZ)诱发实验性糖尿病模型,大鼠随机分为对照组(A组)和糖尿病组(B组),分别在注射STZ后第2、4和6周取材.采用免疫组化检测ADM、ET-1及其受体的表达,Western印迹检测肾上腺髓质素受体(ADMR)和内皮素受体A(EDNR-A)蛋白的表达,RT-PCR检测ADM和ET-1 mRNA的表达.结果 B组较A组ADM的表达先升高后降低,ADMR、ET-1和EDNR-A表达增强.结论 ADM和ET-1及其受体等血管活性物质在DN发病过程发挥着重要的作用.     

氟伐他汀对动脉粥样硬化血管外膜炎症的影响

目的探讨氟伐他汀对实验性动脉粥样硬化(AS)家兔血管外膜炎症的影响及其机制。方法32只新西兰白兔随机分为3组:①对照组8只;②AS模型组12只;③氟伐他汀组12只,喂养12w后处死,取得主动脉标本,用HE染色观察形态学变化和血管外膜炎症细胞浸润情况,用免疫组化染色镜下观察血管外膜成纤维细胞NF-κBp65活性变化。结果正常对照组胸主动脉外膜未见炎性细胞浸润,成纤维细胞胞核内未见NF-κBp65阳性表达。AS组血管外膜可见明显的炎性细胞浸润,成纤维细胞胞核中NF-κBp65阳性表达明显增加。氟伐他汀组血管外膜可见炎性细胞浸润,但较AS组明显减少〔(0.17±0.02)与(0.43±0.19),P=0.003〕,成纤维细胞NF-κBp65有阳性表达,亦较AS组明显减少〔(0.31±0.02)与(0.57±0.04),P=0.002〕。结论氟伐他汀对AS血管外膜炎症的抑制作用可能与抑制成纤维细胞NF-κBp65活性有关。     

肾上腺髓质素对大鼠血管钙化的影响

目的　观察肾上腺髓质素 (ADM)对血管钙化的影响。方法　维生素D3 (VitD3 )和尼古丁制备大鼠血管钙化模型 ,分别测定血管、心肌钙含量和血管碱性磷酸酶 (ALP)活性 ,血浆和血管ADM含量 ,12 5I ADM与ADM受体的结合力及血管环磷酸腺苷 (cAMP)含量。结果　与对照组相比 ,钙化组 (VDN组 )的血管钙含量和ALP活性明显升高 ;血管及血浆ADM的含量亦升高 ,但12 5I ADM与血管质膜ADM受体结合的位点减少 ,Kd值升高 ,提示亲合力降低 ,同时伴钙化血管的cAMP合成减少。提示钙化血管对ADM的反应减弱。空载脂质体对血管钙化无影响。用脂质体包裹ADM组 (VDN ADM组 )与钙化组相比 ,其血管的钙含量、ALP的活性均明显降低 ;12 5　I ADM与血管质膜ADM受体结合的位点增加 ,Kd值减少 ,cAMP的合成也增加 ,提示该组血管对ADM的反应增强。结论　血管钙化时ADM ADM受体 cAMP途径发生变化 ,外源性ADM通过改善ADM ADM受体 cAMP途径 ,发挥抑制血管钙化的作用     

Effects of adrenomedullin on vascular calcification in rats

Objective The aim of the present study was to investigate the effect of adrenomedullin (ADM) on vascular calcification. Methods The vascular calcification model was established in rats (VND group) by using vitamin D₃ (300000IU/kg) and nicotine (25mg/kg, two doses). The effect of liposome-encapsulated ADM was observed. Vascular calcium content, alkaline phosphatase (ALP) activity, ADM in aortic tissue and plasma, binding ability of ¹²⁵I-ADM for ADM receptor on vascular plasma membrane and content of cAMP in vessels were measured. Results Compared with control rats, the aortic calcium content and vascular ALP activity in rats of the VDN group was obviously increased; in addition ADM concentrations in plasma and vessels of rats in VDN group were increased. But the maximum binding sites of ¹²⁵I-ADM for ADM receptor (Bmax) on vascular plasma membrane in rats of VDN group were significantly decreased compared with control rats. The affinity of ¹²⁵I-ADM for the ADM receptor was reduced, as shown by the Kd value and vascular cAMP content being reduced in rats of the VDN group compared to the control group. The in vitro response of isolated vessels to ADM incubation was weakened. Administration of empty liposome had no effect on vascular calcification. But administration of ADM significantly decreased vascular calcium content and ALP activity. The Bmax of ¹²⁵I-ADM for ADM receptors on vascular plasma membrane increased by 17.7% (p<0.01), and the value of Kd decreased by 36.2% (P<0.01) in rats treated with ADM as compared with rats of the VDN group. In addition, the vascular cAMP content and the response to ADM in isolated aorta were markedly increased. Conclusion Vascular calcification induced an alteration of the vascular ADM-ADM receptor-cAMP pathway. Treatment with exogenous ADM inhibited vascular calcification by improving the vascular ADM-ADM receptor-cAMP pathway.     

Effects of adrenomedullin on vascular calcification in rats

OBJECTIVE: The aim of the present study was to investigate the effect of adrenomedullin (ADM) on vascular calcification. METHODS: The vascular calcification model was established in rats (VND group) by using vitamin D3 (300,000 IU/kg) and nicotine (25 mg/kg, two doses). The effect of liposome-encapsulated ADM was observed. Vascular calcium content, alkaline phosphatase (ALP) activity, ADM in aortic tissue and plasma, binding ability of 125I-ADM for ADM receptor on vascular plasma membrane and content of cAMP in vessels were measured. RESULTS: Compared with control rats, the aortic calcium content and vascular ALP activity in rats of the VDN group was obviously increased; in addition ADM concentrations in plasma and vessels of rats in VDN group were increased. But the maximum binding sites of 125I-ADM for ADM receptor (Bmax) on vascular plasma membrane in rats of VDN group were significantly decreased compared with control rats. The affinity of 125I-ADM for the ADM receptor was reduced, as shown by the Kd value and vascular cAMP content being reduced in rats of the VDN group compared to the control group. The in vitro response of isolated vessels to ADM incubation was weakened. Administration of empty liposome had no effect on vascular calcification. But administration of ADM significantly decreased vascular calcium content and ALP activity. The Bmax of 125I-ADM for ADM receptors on vascular plasma membrane increased by 17.7% (p < 0.01), and the value of Kd decreased by 36.2% (P < 0.01) in rats treated with ADM as compared with rats of the VDN group. In addition, the vascular cAMP content and the response to ADM in isolated aorta were markedly increased. CONCLUSION: Vascular calcification induced an alteration of the vascular ADM-ADM receptor-cAMP pathway. Treatment with exogenous ADM inhibited vascular calcification by improving the vascular ADM-ADM receptor-cAMP pathway.     

氟伐他汀预处理对大鼠缺血再灌注损伤心肌的影响

目的：探讨氟伐他汀预处理对大鼠缺血再灌注心肌的作用及其机制。方法：48只SD大鼠被均分为假手术组、缺血再灌注组和氟伐他汀预处理组。采用免疫组化法检测心肌组织中基质金属蛋白酶（MMP）-1,MMP-9及金属蛋白酶组织抑制剂（TIMP）-1的表达,多导生理信号采集系统记录心功能[包括左室收缩压（LVSP）、左室舒张末期压（LVEDP）、左室压最大上升和下降速率（±dp／dtmax）]的改变．以SABC比色法测定血浆中肌酸激酶（CK）、乳酸脱氢酶（LDH）的含量和心肌组织中髓过氧化物酶（MPO）活性,称重法测定心肌梗塞百分比变化。结果：缺血再灌注组心功能[LVSP：（12．87±2．25）kPa,＋dp／dtmax：（379．75±51．40）kPa／s,LVEDP：（1．31±0．14）kPa,-dp／dtmax：（292．21±52．62）kPa／s]明显差于氟伐他汀组[LVSP：（15．71±1．68）kPa,＋dp／dtmax：（534．71±73．99）kPa／s,LVEDP：（1．14±0．12）kPa,-dp／dtmax：（338．45±59．74）kPa／s,P均〈0．01];缺血再灌注组血浆CK、LDH水平和心肌组织MPO活性分别为（319．16±39．07）U／ml、（5249．63±379．53）U／L和（4．21±0．62）U／g,氟伐他汀预处理后上述指标明显降低,分别为（215．55±32．56）U／ml、（3236．48±281．24）U／L,（2．53±0．45）U／g,两组相比差异显著（P均〈0．01）。且氟伐他汀预处理组心肌梗塞面积明显小于缺血再灌注组[（56．20±3．87）％：（68．55±6．46）％,P〈0．05]。此外,与缺血再灌注组相比,氟伐他汀预处理还明显减少心肌组织中MMP-1,-9表达和上调TIMP—1表达（P均〈0．01）。结论：氟伐他汀预处理可减轻大鼠心肌缺血再灌注损伤。     

Effects of TCV-116 on expression of NOS and adrenomedullin in failing heart of Dahl salt-sensitive rats

We examined the effects of TCV-116, an angiotensin II type 1 receptor antagonist, on endothelial-cell nitric oxide synthase (eNOS), inducible NOS (iNOS), and adrenomedullin (ADM) expression in the left ventricle (LV) and evaluated these relation to myocardial remodeling in failing heart of Dahl salt-sensitive hypertensive rats (DS) fed a high-salt diet. TCV-116 (DSHF-T, 5 mg/kg/day, subdepressor dose) or vehicle (DSHF-V) were given from left ventricular hypertrophy to heart failure stage for 7 weeks. Markedly increased left ventricular end-diastolic diameter and reduced fractional shortening in DSHF-V was significantly ameliorated in DSHF-T. The eNOS mRNA and protein in the LV was significantly suppressed in DSHF-V compared with control rats (DR-C), and significantly increased in DSHF-T compared with DSHF-V. The iNOS mRNA and protein, ADM mRNA and immunoreactive ADM contents, and type I collagen mRNA in the LV were significantly increased in DSHF-V compared with DR-C, and significantly decreased in DSHF-T compared with DSHF-V. DSHF-V showed a significant increase of the wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis, with all these parameters being significantly improved by TCV-116. In conclusion, myocardial remodeling and heart failure in DS rats fed a high-salt diet were significantly ameliorated by a subdepressor dose of TCV-116, which may be due to a increased in eNOS and a decreased in iNOS mRNA and protein expression in the LV. Moreover, the ADM mRNA and immunoreactive ADM contents are upregulated in failing heart of DS rats fed a high-salt diet, and increased ADM expression may have a role in the defense mechanism against further cardiac dysfunction and impaired myocardial remodeling.     

壳聚糖对大鼠动脉粥样硬化的影响及其机制探讨

目的:研究壳聚糖对大鼠动脉粥样硬化斑块及一氧化氮合酶(NOS)的影响。方法:40只Wistar大鼠均分为:A组(正常对照组);B组:饲以高脂饲料(不含维生素D3);C组:一次性给予大鼠维生素D3(30万U/kg体重)肌肉注射,以球囊损伤主动脉内皮和饲以含维生素D3(1.25×106U/kg)的高脂饲料;D组在C组的基础上饲料中加入5%壳聚糖。90 d后检测主动脉动脉粥样硬化斑块形成及NOS的活性。结果:(1)90 d后C组大鼠胸主动脉形成了明显的动脉粥样硬化斑块,而仅饲以高脂饲料的大鼠胸主动脉结构未见改变,D组大鼠胸主动脉未形成动脉粥样硬化斑块;(2)血管中内皮型一氧化合酶(eNOS)后三组较A组均活性下降(P<0.01),而三者之间无统计学差异;(3)诱导型一氧化氮合成酶(iNOS):B组较A组无差异,而C组较A、B两组表达和活性均显著增加(P<0.05~<0.01),较之C组,D组的水平下降(P<0.01),但仍高于A、B组(P<0.01);(4)较之A组,B、C组的TC、TG、LDL-C水平上升(P<0.05~<0.01),D组的较C组下降(P<0.05~<0.01);B、C组的HDL-C水平较A组明显下降(P<0.01)。结论:壳聚糖可通过抑制胆固醇、甘油三酯等的吸收而发挥抗动脉粥样硬化作用,并通过对血脂的作用而间接发挥对NOS的影响。     

酮替芬对Wistar大鼠动脉粥样硬化的干预研究

目的观察酮替芬(Ket)对动脉粥样硬化形成的干预作用。方法将40只雄性Wistar大鼠随机分为4组,即A组[高脂+维生素D_3(VitD_3)]、B组[高脂+VitD_3+Ket]、C组[高脂+VitD_3+卵蛋白(OVA)]和D组(高脂+VitD_3+OVA+Ket)。A组常规建立动脉粥样硬化模型,C组在常规高脂的基础上加用OVA激活肥大细胞建立动脉粥样硬化模型,B、D两组分别在A、C组建立动脉粥样硬化的过程中给予Ket干预。实验完毕后,分别对A、B组以及C、D组斑块病理形态及斑块中肥大细胞的分布情况进行比较。结果 (1)A、C组动脉粥样硬化病理改变分别较B、D组为重,可见典型AS及不稳定AS改变;B、D组Ket药物干预达到预期效果;(2)动脉粥样硬化斑块中的肥大细胞分布密度A组比B组:5.00±1.41比2.88±1.25,P<0.05;C组比D组:8.00±1.29比5.86±2.03,P<0.05,差异均有统计学意义;(3)实验结束时测定大鼠血清白介素(IL)-6水平,A组比B组:(60.18±8.15)ng/L比(41.52±6.71)ng/L,P<0.05;C组比D组:(90.66±8.18)ng/L比(68.32±5.92)ng/L,P<0.05,差异均有统计学意义。结论高脂+VitD_3+OVA能够建立较为成熟、更符合人类动脉粥样硬化病理形态的大鼠模型;肥大细胞在动脉粥样硬化的形成中有着重要作用,是动脉粥样硬化形成的重要炎症细胞;全身性的肥大细胞活化对斑块形成有促进作用;Ket有抑制炎症因子活化的作用,对斑块形成及失稳定有预防作用。     

肝肺综合征大鼠肾上腺髓质素及其受体的表达

目的 探讨肾上腺髓质素(ADM)在肝肺综合征(HPS)发病机制中的作用。方法 采用Wistar大鼠行胆总管结扎术(CBDL)制备HPS动物模型，进行血气分析，使用放射免疫方法检测血浆和肺组织匀浆中ADM水平；采用RT-PCR方法检测肺组织中ADM mRNA及其特异性受体Ll mRNA的表达。结果(1)从术后第3周至第5周，CBDL组大鼠血浆和肺组织中ADM水平动态升高；(2)CBDL 5周组大鼠肺组织中ADM mRNA的表达较对照组升高，差异有显著性(P＜0．05)，而两组间Ll mRNA的表达差异无显著性(P＞0．05)；(3)相关分析表明，各阶段血浆和肺组织ADM水平均与天冬氨酸转氨酶(AST)、门静脉压力、肺泡-动脉氧分压差(A-aDO2)呈正相关，出现腹水者血浆和肺组织ADM水平高于未出现腹水者。结论 在HPS形成过程中，血浆和肺组织中扩血管物质ADM水平持续升高，与肝功能受损状态、门脉压力升高程度、腹水形成及PaO2降低有关，提示ADM增多可能参与HPS时肺内血管扩张(IPVD)的发生。     

Estrogen and phytoestrogen regulate the mRNA expression of adrenomedullin and adrenomedullin receptor components in the rat uterus

The serum estrogen surge in the uterus triggers precisely-timed physiological and biochemical responses required establishing and maintaining pregnancy. Previous reports have shown that consumption of phytoestrogen-containing plants may disrupt the precise control of pregnancy. To evaluate the effects of phytoestrogens in the uterus, we screened for estradiol (E2)-inducible genes in immature rat uteri. We identified the gene for receptor-activity-modifying protein 2 (Ramp2), known to be a component of the adrenomedullin (ADM) receptor, as responsive to both E2 and the phytoestrogen coumestrol (Cou). We further examined the expression of ADM and ADM signaling components Ramp2, Ramp3, and CRLR in the immature rat uterus and found that both E2 and Cou regulated these genes expression. In addition, treatment with ADM increased uterine weight and edema similar to that observed after Cou treatment. Our findings indicated that the phytoestrogen caused the abnormal induction of vasoactive factors in the uterus.