雌激素提高去卵巢大鼠海马CA4区ERK1/2的磷酸化水平

目的研究雌激素对去卵巢大鼠海马CA4区神经元细胞外信号调节激酶1／2（ERK1／2）磷酸化水平的影响。方法成年Wistar雌性大鼠随机分为正常对照组（INT）、去卵巢组（OVX）和去卵巢加雌激素组（OVX＋estrogen）。用放射免疫分析方法测定血中雌二醇含量，用免疫组化检测ERK1／2的磷酸化水平。结果去卵巢组大鼠体内雌激素水平明显降低，与对照组和加雌激素组比较均有显著性差异（P〈0．001）；采用免疫组织化学定位检测，显示磷酸化ERK1／2主要表达在神经元胞核和胞质；免疫组化阳性细胞统计分析显示：去卵巢组大鼠海马CA4区神经元胞核和胞质着色浅，ERK1／2磷酸化水平降低，其阳性细胞计数明显减少，与对照组比较有显著性差异（P〈0．001）；去卵巢加雌激素组与去卵巢组相比，海马CA4区神经元胞核和胞质染色深，磷酸化ERK1／2表达阳性神经元增多（P〈0．001），但仍明显低于对照组。结论雌激素提高衰老雌性大鼠脑内ERK1／2磷酸化水平，提示雌激素可通过对衰老状态下ERK信号通路的调节作用达到改善学习和记忆的目的。     

脑源性神经营养因子在孤独症模型鼠颞叶皮层中的表达

目的研究颞叶皮层脑源性神经营养因子(BDNF)表达与孤独症的关系。方法孕12.5 d Wistar 大鼠腹腔注射丙戊酸钠(VPA) 600 mg/kg,观察仔鼠(VPA组)的行为学特征,应用免疫组化法检测VPA组与对照仔鼠(对照组,腹腔注射等量生理盐水)颞叶皮层BDNF 表达。结果与对照组相比,VPA 组表现为低体重(P<0.05),睁眼时间延迟(P<0.05),协调性反应差(P<0.05),方向趋向性反应迟缓(P<0.05);社交行为次数减少(P<0.05)、潜伏期延长(P<0.05)、持续时间缩短(P<0.05),重复行为增多(P<0.05)。小脑浦肯野细胞数量减少。出生后1 d、7 d、14 d 时,VPA 组颞叶皮层BDNF 表达明显高于对照组(P<0.01),而出生后35 d、49 d 时,VPA组颞叶皮层BDNF 表达明显低于对照组(P<0.01)。结论颞叶BDNF 表达参与孤独症的发病过程。     

电针对去卵巢大鼠脑内雌激素受体mRNA的影响

目的探讨雌激素降低对脑内雌激素受体基因表达的影响以及电针刺激足三里穴对去卵巢大鼠脑内雌激素受体基因表达的调整作用。方法选用成年Wistar雌性大鼠，将动物分为正常对照组（INT）、去卵巢组（OVX）和去卵巢针刺组（OVX＋EA）。用放射免疫分析方法测定血中雌二醇和睾酮的含量，采用RT-PCR方法获得大鼠雌激素受体α（ERα）和雌激素受体β（ERβ）mRNA的逆转录表达产物cDNA，用琼脂糖凝胶电泳方法检测，计算机图像分析系统进行统计分析。结果与对照组比较，去卵巢组大鼠血中雌二醇水平明显降低（P〈0．01），同时伴有睾酮升高，脑内ERα mRNA的RT-PCR表达产物减少（P〈0．01），ERβ mRNA的RT—PCR表达产物增加（P〈0．01）；与去卵巢组相比，去卵巢针刺组大鼠血中雌激素水平明显升高（P〈0．01），睾酮水平下降（P〈0．01），脑内ERα mRNA的RT-PCR产物升高（P〈0．01），ERβ mRNA的RT—PCR产物降低（P〈0．01）。结论去卵巢大鼠血中雌激素水平降低，睾酮水平升高，脑内ERα和ERβ mRNA的表达发生了明显的变化；电针足三里穴对体内雌激素和睾酮水平及脑内雌激素受体基因表达有明显的调整作用，这可能是电针调节神经内分泌功能的机制之一。     

雌激素抑制SD雌性大鼠下丘脑弓状核kisspeptin表达

目的:探讨雌激素对SD雌性大鼠弓状核kisspeptin基因表达的影响。方法:将15只SD雌性大鼠随机分成3组即正常对照组、卵巢切除(OVX)组、卵巢切除并行激素替代治疗(OVX+E2)组,通过免疫组化方法对3组雌性大鼠的下丘脑弓状核kiss1-ir细胞进行计量分析。结果:OVX组SD大鼠下丘脑kiss1-ir细胞明显较其他两组增多(P<0.01),而正常对照组与OVX+E2组无明显差异。结论:去卵巢大鼠的kisspeptin-ir细胞明显增加,而尼尔雌醇替代后kisspeptin-ir细胞减少。雌激素明显抑制SD雌性大鼠弓状核kisspeptin表达。     

雌激素对去势大鼠骨组织不同部位骨保护素表达的影响

目的 观察骨保护素(OPG)在去卵巢骨质疏松模型大鼠骨组织不同部位的表达变化及雌激素对其的干预作用.方法 SD 雌性大鼠随机分为假手术组(SHAM)、模型组(OVX)、雌激素组(OVX +E2),观察骨组织形态学变化,检测血清雌二醇(E2)及碱性磷酸酶(AKP)、抗酒石酸酸性磷酸酶(TRAP)水平,观测OPG 在股骨干骺端不同部位的表达.结果 与SHAM 组比较,OVX 组骨小梁稀疏,排列紊乱,骨小梁间隙明显增大,血清E2 水平显著下降(P ＜0.01),AKP、TRAP 均明显升高(P ＜0.05),OPG 在股骨干骺端关节软骨、骺板下初级小梁骨的表达均有升高趋势(P ＞0.05);与OVX 组相比,OVX +E2 组骨小梁排列相对整齐,密度、厚度明显增加,E2 水平显著增高(P ＜0.01),AKP、TRAP 水平明显降低(P ＜0.05),OPG 表达均显著升高(P ＜0.01).结论 雌激素可通过调控OPG 在骨组织中的表达发挥抗骨质疏松作用.     

乙醇诱导大鼠脑损伤时小脑维生素D依赖性钙结合蛋白28K表达及山莨菪碱的影响

目的 探讨乙醇诱导大鼠脑损伤时小脑维生素D依赖性钙结合蛋白28K(CaBP)表达及山莨菪碱的保护作用.方法 2月龄SD雄性大鼠分别腹腔注射生理盐水、乙醇、山莨菪碱 生理盐水、山莨菪碱 乙醇(均n=18),8 d后行Morris水迷宫测试,免疫组化结合图像分析系统计数小脑CaBP阳性表达的蒲肯野细胞平均面积百分比和灰度值.结果 乙醇组Morris水迷宫潜伏期较其他3组延长(P《0.05),游泳距离较生理盐水组和山莨菪碱 生理盐水组延长(P《0.05),与山莨菪碱 乙醇组有延长的趋势,但无显著性差异(P》0.05).乙醇组小脑CaBP阳性表达的蒲肯野细胞计数、平均阳性细胞面积百分比和灰度值均少于其他3组(P《0.05),山莨菪碱 乙醇组阳性细胞数与生理盐水组和山莨菪碱 生理盐水组无显著性差异(P》0.05),但平均阳性细胞面积百分比和灰度值降低(P《0.05).结论 乙醇可使小脑蒲肯野细胞的CaBP的表达减少;山莨菪碱对此具有一定保护作用.     

植物雌激素对去卵巢血管性痴呆大鼠认知功能和海马胆碱乙酰转移酶表达的影响

目的:观察植物雌激素对去卵巢血管性痴呆(VD)大鼠海马胆碱能神经元表达的影响,探讨植物雌激素对去卵巢VD大鼠的脑保护作用及可能机制。方法:60只雌性Wistar大鼠经水迷宫筛选随机分为4组。Ⅰ组(sham组):VD大鼠,未去除卵巢;Ⅱ组(OVX组):VD大鼠,去除卵巢;Ⅲ组(OVX+est组):VD大鼠,去除卵巢,给予化学雌激素喂养;Ⅳ组(OVX+phy组):去除卵巢,给予植物雌激素喂养。4组大鼠VD手术前后分别应用Morris水迷宫检测法进行大鼠空间认知功能的评价。采用胆碱乙酰转移酶(ChAT)免疫组织化学ABC法,观察去卵巢VD大鼠各组海马胆碱能神经元的数目。结果:与OVX组相比,OVX+est组及OVX+phy组的大鼠海马胆碱能神经元数目明显升高(P<0.05),且在水迷宫中找到水下平台的时间、距离明显缩短(P<0.05),而与sham对照组差别不明显,且OVX+est组和OVX+phy组相比较,无显著性差异(P>0.05)。结论:植物雌激素具有雌激素样作用,能增强大鼠海马胆碱能神经元的ChAT表达,对血管性痴呆大鼠的记忆损害有一定程度的保护作用。     

三仙汤治疗去卵巢骨质疏松模型大鼠的实验研究 证据显示此项目对雌激素及相关指标无影响对骨生物力学性能作用较强

目的通过研究三仙汤对去卵巢大鼠骨密度(BMD)、骨生物力学和血清雌二醇(E2)、孕酮(P)水平等的影响,探讨三仙汤治疗骨质疏松的机制。方法68只3月龄雌性SD大鼠随机分为7组:空白组、假手术组(Sham)、模型组(OVX)、尼尔雌醇组、以及三仙汤小、中、大3个剂量组。给药3个月后测定BMD、最大载荷(E)、破坏挠度(R)、E2、P、体质量和子宫湿重。结果骨密度:OVX组0.270g/cm2,显著低于Sham组0.291g/cm2(P<0.05),三仙中剂量较OVX有上升趋势。最大载荷:三仙中剂量117kg、大剂量组114kg与OVX组104kg相比有一定的上升趋势。破坏挠度:OVX组较Sham组下降趋势明显;三仙小、中、大3个剂量组均较OVX组显著升高(P<0.05);三仙中剂量组0.881mm较尼尔雌醇组0.737mm也显著升高(P<0.05)。E2、孕酮及子宫湿重:OVX组显著低于Sham组(P<0.001),尼尔雌醇组显示一定的升高趋势,三仙各组与OVX相比差异无显著性意义。体质量:OVX组400g较Sham组347g显著上升(P均<0.05);尼尔雌醇组较OVX组及三仙各组显著减轻(P<0.001);三仙各组与OVX相比无明显变化。结论尼尔雌醇对去卵巢大鼠骨密度和骨结构的改善无明显作用;三仙汤能够改善去卵巢大鼠骨生物力学性能,对OVX大鼠雌激素水平无明显影响。     

TGF-β和ERK在骨质疏松大鼠骨组织中的表达

目的:研究转化生长因子(TGF-β)和信号调节激酶(ERK)在去卵巢大鼠骨组织中的表达及意义。方法:30只2月龄SD雌性大鼠分别造模为假手术组(SHAM组)、卵巢切除组(OVX组)及雌激素替代组(OVX-N组)各10只,用免疫组化法测定成骨细胞中TGF-β和磷酸化ERK的表达并进行定量分析。结果:TGF-β蛋白阳性表达主要在成骨细胞的胞膜上和胞浆内,ERK主要在成骨细胞核内,OVX-N组TGF-β和ERK的阳性表达高于OVX组(P<0.01,0.05),与SHAM组比较差异不明显。结论:TGF-β和ERK可能在绝经后骨质疏松症中起重要调节作用。     

机械振动对去卵巢后骨质疏松骨折大鼠雌激素和脑源性神经营养因子表达的影响

目的 探讨机械振动对去卵巢后骨质疏松骨折大鼠海马雌激素和骨折端脑源性神经营养因子（BDNF）表达的影响。 方法 选取3月龄雌性Wistar大鼠30只,按照随机数字表法将其分为对照组、去卵巢组、振动组,每组10只。对照组建立骨折模型,去卵巢组和振动组建立去卵巢后骨质疏松骨折模型,采用频率35 Hz、每日20 min、每周5 d的全身垂直振动作用于振动组。干预2周和6周后,采用X线评价各组大鼠的骨折愈合情况,并通过酶联免疫吸附实验和免疫印记法分别检测大鼠海马雌激素、骨折端BDNF的含量。 结果 干预2周和6周后,振动组大鼠骨折愈合率较对照组和去卵巢组高（P＜0.05）。振动组大鼠干预2周和6周后的海马雌激素含量［（0.72±0.03）ng/ml、（1.19±0.03）ng/ml］较对照组和去卵巢组高（P＜0.05）,干预2周和6周后的骨折端BDNF含量［（0.26±0.01）ng/ml、（0.39±0.06）ng/ml］较对照组低、较去卵巢组高（P＜0.05）。大鼠骨折端BDNF表达水平与其骨折愈合率高度相关。 结论 机械振动可以促进大鼠海马雌激素和骨折端BDNF表达,加速去卵巢后骨质疏松大鼠骨折愈合。     

普萘洛尔对去卵巢大鼠骨密度及血清白细胞介素6的影响

背景交感神经系统影响骨代谢的具体作用和机制不明确.目的探讨普萘洛尔对去卵巢大鼠骨密度及对血清白细胞介素6(IL-6)水平的影响,研究B受体阻滞剂对骨质疏松的防治作用及机制.设计随机对照的实验研究.地点、材料和干预本实验在中国中医研究院基础所完成.将50只健康雌性未交配6个月龄SD大鼠随机分为5组①假手术组.②去卵巢(OVX)后雌激素治疗(O+E)组.③OVX后普萘洛尔治疗(O+P)组.④OVX后雌激素+普萘洛尔治疗(O+E+P)组.⑤OVX后安慰剂(OVX)组.OVX后l周开始经灌胃给予普萘洛尔、皮下注射17β-雌二醇,共12周.动物处死时留取第3～5腰椎、血清标本,进行骨密度分析及血清IL-6水平测定.主要观察指标各组大鼠椎骨骨密度及血清瘦素水平.结果O+P,O+P+E O+E组的骨密度较OVX组明显增高(P＜0.05),血清IL-6水平OVX组[(336.6±18.1)ng/L]较假手术组[(208.8±17.2)ng/L]明显增高(t=16.982,P＜0.01),O+E组[(252.7±16.3)ng/L],O+P组[(274.4±20.0)ng/L],O+P+E组[(222.9±16.5)ng/L]均明显低于OVX组[(336.6±18.1)ng/L](t=11.160,7.783,14.971,P＜0.01).结论普萘洛尔能使卵巢切除术后骨质疏松大鼠的骨密度改善,能有效地预防OVX大鼠的骨丢失,同时降低血清IL-6水平.     

Estrogen and progesterone prevent disruption of prepulse inhibition by the serotonin-1A receptor agonist 8-hydroxy-2-dipropylaminotetralin

The aim of the present study was to investigate the effect of estrogen and progesterone treatment on 5-hydroxytryptamine (serotonin)-1A (5-HT(1A)) receptor-mediated disruption of prepulse inhibition (PPI) of acoustic startle. The age-at-onset of schizophrenia is later in women than men, and it has been suggested that women may be protected from schizophrenia by the sex steroid hormone estrogen. 5-HT(1A) receptors have been implicated in the development of schizophrenia and the action of antipsychotics. PPI is a model of sensorimotor gating that is deficient in schizophrenia and other illnesses. Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Some OVX rats received silastic implants filled with a low dose of estrogen (E20), a high dose of estrogen (E100), progesterone (P), or both the E20- and P-filled (E/P) silastic implants. Two weeks later, the rats were randomly treated with saline, or 0.02 or 0.5 mg/kg of the 5-HT(1A) receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). Treatment with 8-OH-DPAT resulted in a dose-dependent increase in startle amplitude in all rat groups. PPI was significantly reduced after injection of 0.5 mg/kg 8-OH-DPAT in sham-operated rats, untreated OVX rats, E20-treated OVX rats, and P-treated OVX rats. In contrast, in E100- and E/P-treated OVX rats, PPI was not significantly reduced by 0.5 mg/kg 8-OH-DPAT. These data suggest that treatment with a high dose of estrogen, or with a combination of estrogen and progesterone, prevents 8-OH-DPAT-induced disruption of PPI. Thus, these hormones could be protective against sensorimotor gating deficits, at least those induced by 5-HT(1A) receptor stimulation, and may therefore be beneficial against some symptoms of schizophrenia.     

Sex-specificity and estrogen-dependence of kappa opioid receptor-mediated antinociception and antihyperalgesia

This investigation determined whether the activation of the kappa opioid receptor (KOR) in the spinal cord produces estrogen-dependent, sex-specific modulation of acute and inflammation-induced persistent nociception. We demonstrate for the first time that KOR antinociception and gene expression are enhanced by exogenous or endogenous estrogen in the female. The lack of KOR antinociception and KOR gene expression are not altered by the hormonal status (testosterone or estrogen) in males. Cannulae were implanted intrathecally in male, gonadectomized male (GDX), intact and ovariectomized female (OVX) Sprague-Dawley rats. Estradiol was injected subcutaneously, 48 h before testing (GDX+E and OVX+E). Intrathecal injection of U50,488H, a selective KOR agonist, dose dependently increased heat-evoked tail flick latencies (TFLs) in proestrous and OVX+E groups, but not in male, GDX, GDX+E, OVX, and diestrous groups. Further, estrogen dose-dependently enhanced the effect of U50,488H in OVX rats. KOR selective antagonist, nor-binaltorphimine (Nor-BNI), blocked the antinociceptive effect of U50,488H. U50,488H reversed the carrageenan-induced thermal hyperalgesia in OVX+E rats, but not in male or OVX rats. However, U50,488H treatment did not alter mechanical thresholds in any group, with or without inflammation. KOR gene expression was enhanced in proestrous and OVX+E groups as compared to any other group. We conclude that selective activation of KOR in the spinal cord produces sex-specific, stimulus- and estrogen-dependent attenuation of acute and inflammatory pain in the rat via estrogen-induced upregulation of the KOR gene expression in the spinal cord. These findings may further implicate estrogen dependence of KOR effects in learning, epilepsy, stress response, addiction etc.     

运动对Ⅰ型原发性骨质疏松症形成的干预

目的观察运动对去卵巢雌性大鼠骨密度的影响。方法雌性SD大鼠随机分为空白组、去卵巢组、雌激素组及运动组。用双能X线骨密度测量仪,测量大鼠的全身及腰椎部骨密度,并称量大鼠体重和子宫重量。结果运动能抑制骨质疏松大鼠骨量的丢失和体重的增长(P<0.05),运动组大鼠的子宫系数明显低于雌激素组(P<0.01),与去卵巢组近似。结论运动对绝经后骨质疏松症的形成有一定干预作用。     

Effects of estrogen on platelet reactivity after transient forebrain ischemia in rats

Estrogen's prothrombotic effects are of increasing concern, particularly in stroke risk and recovery. Using an ischemic rodent model, the authors sought to determine (a) if estrogen replacement increases postischemic platelet reactivity, (b) if changes in estrogen status alter intraplatelet endothelial nitric oxide synthase (eNOS) synthesis, and (c) if estrogen-mediated effects on platelets alter cerebral blood flow during reperfusion. Intact (I), ovariectomized (OVX), and OVX + 17 beta-estradiol (E50) rats were subjected to 30 min of forebrain ischemia and 60 min of reperfusion. Using the platelet activation marker P-selectin, postischemic platelet reactivity was quantified by flow cytometry. In a separate cohort (I, OVX, E50), the authors quantified platelet eNOS by Western blot. Another cohort (OVX, E50) was subjected to ischemia/reperfusion, and cerebral blood flow was determined using the iodoantipyrine technique. Collagen-stimulated platelet P-selectin expression was increased in the OVX rats at 60 min of reperfusion, and this effect was reversed by estrogen treatment. No differences in platelet eNOS expression were detected among groups. Cerebral blood flow at 60 min reperfusion was comparable between the OVX and the E50 rats. The authors conclude that during reper-fusion, estrogen deficiency increases postischemic platelet sensitivity to stimuli in estrogen-deficient rats. Estrogen treatment mitigates effects of estrogen loss on platelets, but this early effect is apparently not caused by intraplatelet eNOS depression. Neither estrogen deficiency nor estrogen treatment changes early postischemic regional brain blood flow. In this rodent global cerebral ischemic model, physiologic doses of estrogen are not deleterious to platelet reactivity and may initially reduce postischemic platelet reactivity.     

电针对阿尔茨海默病大鼠学习记忆能力及前额叶P35/P25-周期蛋白依赖性激酶5-Tau蛋白磷酸化通路的影响

目的 观察电针百会、肾俞两穴对阿尔茨海默病(AD)模型大鼠学习记忆能力及前额叶皮质(PFC) P35/P25-周期蛋白依赖性激酶5 (CDK5)-Tau蛋白磷酸化信号通路的影响,以探讨电针治疗AD的相关机制。方法 雄性成年Sprague-Dawley大鼠随机分为正常对照组、假手术组、模型组和电针组,每组6只。后两组双侧海马注射Aβ_25-35,假手术组注射等量生理盐水。造模后次日,电针组电针百会、肾俞,留针15 min,每天1次,共10 d。治疗后,行Morris水迷宫实验,免疫组织化学染色和Western blotting检测各组PFC P35/P25-CDK5-Tau蛋白磷酸化相关蛋白的表达情况。结果 与正常对照组和假手术组比较,模型组的逃避潜伏期和搜索路径均增加(P < 0.05),穿越平台次数减少( P < 0.05);与模型组比较,电针组逃避潜伏期和搜索路径均缩短( P < 0.05),穿越平台次数增加( P < 0.05)。模型组P35/P25和CDK5阳性表达明显高于正常对照组和假手术组( P < 0.01),电针组显著低于模型组( P < 0.001)。模型组P35/P25、CDK5、Tau[pS199]、Tau[pS202]相对表达量高于正常对照组和假手术组( P < 0.05),电针组上述蛋白的表达低于模型组( P < 0.05)。 结论 电针刺激能有效改善AD大鼠的学习记忆和空间探索能力,可能通过影响大鼠PFC的P35/P25-CDK5-Tau蛋白磷酸化信号通路,延缓AD的发生与发展。     

Comparison of calcitonin, alendronate and fluorophosphate effects on ovariectomized rat bone.

The effects of calcitonin, alendronate and fluorophosphate preventive treatment on ovariectomized rat femur were studied by comparing densitometric, mechanical, mineralogical and histomorphometric data. Sixty retired breeder female Sprague-Dawley rats, aged 10 months, were randomly divided into six groups. A group (baseline) was euthanized at the beginning of the study as a baseline group; four groups were ovariectomized and one was sham-operated (sham) and considered as a sham-aged group. A group of ovariectomized rats was used as a sham-therapy control (OVX) and received only deionized drinking water, while the other three received: a) salmon calcitonin (SCN) at a dose of 2 IU/kg/d s.c. (OVX + SCN); b) alendronate sodium salt (ALN) at a dose of 6 microg/kg/d administered by gavage (OVX + ALN); and c) L-glutamine monofluorophosphate (G-MFP) and calcium at a rate of 1:30 F/Ca at a dose of 0.21 mg F/6.30 mg Ca per kg/d by gavage (OVX + MFP). Significant increases (P < 0.05) of about 15 and 27% in femoral proximal epiphysis bone mineral density (BMD) of the OVX + ALN group were observed versus healthy groups and the OVX group, respectively. The OVX + ALN group also showed significant increases in femoral mid-diaphysis BMD when compared to OVX (18%, P < 0.001), OVX + SCN (14%, P < 0.05) and OVX + MFP (18%, P < 0.001) groups. In the OVX + MFP group, the three-point bending test demonstrated significant increases (P < 0.05) in maximal load of 21 and 22% when compared to the OVX and OVX + SCN groups, respectively. Also, stiffness data showed significant increases of the OVX + MFP (17%) and sham (14%) groups in comparison with the OVX group. A decrease in Mg (42%, P < 0.05), and increases in Ca (15%, P < 0.0001) and PO4 (8%, P < 0.005) content were found by comparing OVX + MFP and OVX groups. Trabecular bone volume results showed significant increases by comparing OVX + ALN and OVX groups (12.20%, P < 0.0005), as well as control groups. Tested agents were able to reduce the bone loss due to estrogen deficiency, but this did not always produce an increase in strength of the treated bone. Alendronate treatment prevented a decrease in bone mineral density and maintained bone mechanical properties after ovariectomy without impairment of bone mineralization in aged rats.     

Estrogen alters relative contributions of nitric oxide and cyclooxygenase products to endothelium-dependent vasodilation.

The purpose of this study was to determine the effects of in vivo estrogen manipulations on mechanisms of endothelium-dependent vasodilation. Ovary-intact, ovariectomized (OVX), or OVX with estrogen replacement (OVX + E(2)) female Sprague-Dawley rats were studied (n = 8). Mesenteric arteries (approximately 300 microm) were isolated, cannulated, and pressurized to 60 mm Hg in an arteriograph containing bicarbonate buffer and vessel diameter was monitored. Concentration-response curves to the endothelium-dependent histamine H(1) agonist 2-thiazolylethylamine (2-TEA; 1 nM-100 microM) and to acetylcholine (1 nM-10 microM) were performed in preconstricted arteries. The effect of Nomega-nitro-L-arginine (LNA; 100 microM) or LNA + indomethacin (INDO) (10 microM) on agonist-induced vasodilation was determined. There was no difference between treatment groups in the sensitivity of mesenteric arteries to 2-TEA or acetylcholine. LNA produced a significant decrease in sensitivity to 2-TEA in arteries from ovary-intact and OVX + E(2) rats but not in those from OVX rats. The addition of INDO produced a small additional decrease in sensitivity to 2-TEA in arteries from ovary-intact rats, a significant decrease in OVX, and no shift in OVX + E(2). LNA + INDO produced a similar degree of inhibition of the 2-TEA response in the three treatment groups. In contrast, when acetylcholine was used, the decrease in sensitivity produced by LNA or LNA + INDO was similar in the three rat groups. We conclude that estrogen increases the nitric oxide component of endothelium-dependent dilation and decreases the cyclooxygenase component. These effects of estrogen appear to be agonist-specific. Our findings suggest that estrogen modulates cross talk between the nitric oxide synthase and cyclooxygenase pathways of vasodilation.