卵巢过度刺激综合征动物模型制备

目的　构建卵巢过度刺激综合征 (ovarianhyperstimulationsyndrome ,OHSS)的大鼠模型。方法　 18只雌性Wistar大鼠 ,2 2日龄 ,体重 4 2 0～ 5 0 0 g ,随机分成超排卵组 1、组 2和对照组。卵巢过度刺激组从 2 2～ 2 5日龄连续 4d皮下注射马促性腺激素 (eCG) 10IU(0 1ml生理盐水稀释 ) ,在第 2 6日龄皮下注射绒毛膜促性腺激素 (hCG) 30IU、10 0IU ;对照组从第 2 2～ 2 6日龄连续 5d注射生理盐水。在hCG注射 4 8h后 (即 2 8日龄 )尾静脉注射 1%EB(Evensblue)染料 0 1ml,6 0min后腹腔灌注 5ml生理盐水 ,回收灌注液并置一个含有 5 0 μl0 1NNaOH的试管中 ,双侧卵巢分别称重后 ,把左侧卵巢置于 4ml甲酰胺中萃取EB。结果　卵巢过度刺激综合征组卵巢重量组 1为 (4 0 0 5 0±5 1 0 6 )mg ;组 2 (4 2 1 83± 88 93)mg ,显著高于对照组的 (32 82± 5 2 0 )mg(P <0 0 1)。卵巢EB浓度组 1为 (73 18± 11 38)ng/mg ;组 2 (73 2 6± 18 4 4 )ng/mg ,显著高于对照组 (35 87± 5 14 ) ng/mg(P <0 0 1)。组 1腹腔EB浓度 (13 994± 0 4 5 6 ) μg/ml,组 2 (4 15 4± 1 0 90 ) μg/ml,显著高于对照组 (0 333± 0 0 82 ) μg/ml(P <0 0 1)。 结论　利用适当日龄Wister大鼠构建OHSS动物模型成功。     

立体定向建立大鼠C6脑胶质瘤模型

目的　建立大鼠C6脑胶质瘤模型 ,采用影像学方法观察肿瘤的生长规律和时间窗 ,为肿瘤的疗效检测提供可行的方法。方法　 16只SD大鼠随机分成两组 ,每组 8只 ,用立体定向技术将C6细胞接种在大鼠的右侧尾状核 ,接种细胞量分别为 1 0× 10 6 个 (第 1组 )和 1 5× 10 6 个 (第 2组 )。观察大鼠生存期 ,测量肿瘤的最大径 ,计算肿瘤体积 ,计算观察时间窗。结果　两组大鼠皆成功接种肿瘤 ,成功率为10 0 %。第 1组大鼠平均生存期为 ( 2 3 5 0± 3 93 )d ,明显大于第 2组 ( 17 75± 2 3 8)d(P <0 0 1)。肿瘤最大直径与瘤龄呈直线关系 ,体积与瘤龄呈指数关系。观察时间窗第 1组为 ( 12 0 0± 3 5 1)d ,大于第 2组 ( 8 88± 1 73 )d(P <0 0 5 )。结论　立体定向脑内定量注射C6细胞制作大鼠脑胶质瘤模型成功率高 ,肿瘤最大径和体积增长有规律性。观察时间窗能够满足一般的研究要求     

七氟烷吸入麻醉对新生大鼠海马神经发生和认知功能发育的影响

目的探讨七氟烷吸入麻醉对新生大鼠海马神经发生和认知功能发育的影响。方法 7日龄SD大鼠64只,随机分为4组(n=16)。A组吸入40%氧气1 h,B、C、D组分别吸入1.0%、2.0%、4.0%七氟烷1 h。各组取8只大鼠,隔日予5-溴脱氧尿核苷(BrdU)50 mg.kg-1,ip,共3次。于14 d采用免疫组化评分(IHS)评估BrdU标记增殖细胞,观察4组海马神经发生情况。各组余8只大鼠于7 wk末采用Morris水迷宫测试其认知功能。结果 B、C、D组大鼠海马区BrdU阳性细胞IHS分别为2.74±0.40、2.30±0.20、2.30±0.31,A组为4.00±0.36,B、C、D组均低于A组(均P<0.05)。B、C、D组Morris水迷宫测试逃避潜伏期和探索时间均长于A组(P<0.05),且呈剂量依赖性。结论七氟烷吸入麻醉能抑制新生大鼠海马神经发生,并阻抑新生大鼠认知功能发育。     

浙江3市儿童血清中脂溶性维生素水平比较

目的:比较浙江3市儿童血清中脂溶性维生素水平。方法:以高效液相色谱法测定血清中脂溶性维生素浓度。结果:274份血样维生素E、维生素A和β-胡萝卜素含量分别为(9．02±2．36)、(0．53±0．10)、(0．23±0．16)μg·mL-1;25-羟基维生素D3和维生素D3检出率分别为75．55％、51．10％,检出浓度分别为(18．51±7．64)、(20．83±10．67)ng·mL-1。5种脂溶性维生素水平没有性别差异(P>0．05),但地区间差异明显(P<0．01或P<0．05)。结论:浙江3市儿童血清中维生素E、维生素A和β-胡萝卜素营养状况比较理想,但25-羟基维生素D3与维生素D3偏低较为普遍。     

异种肝细胞移植对大鼠药物性肝衰存活率和肝功能的影响

目的　观察异种肝细胞移植对大鼠药物性肝衰的存活率和肝功能的影响。方法　豚鼠为供体 ,海藻酸钠 氯化钡法微囊化。SD大鼠为受体 ,氨基半乳糖腹腔内一次性注射制作肝衰模型。 4 8h后将微囊化豚鼠肝细胞 (1 5× 10 7个 )移植于大鼠脾脏内。豚鼠裸肝细胞 (1 5× 10 7个 )移植及生理盐水 1 2ml脾脏注射为对照。移植后观察受体大鼠 14d存活率和肝功能的改变。结果　微囊化肝细胞移植组存活率 80 % ,明显高于生理盐水组 (2 5 % )和裸肝细胞移植组 (70 % ) (P <0 0 1与P <0 0 5 )。微囊化肝细胞移植组 14d总胆红素 (0 6 8± 0 0 5 μmol/L)和ALT(5 5± 6 7U/L) ,明显低于生理盐水组 (0 82± 0 0 7μmol/L和 91 0± 8 0U/L)和裸肝细胞组 (0 76± 0 0 6 μmol/L和 74 0±7 1U/L) (P <0 0 5和P <0 0 1)。总蛋白 (117 0± 8 4 g/L)和球蛋白 (6 6 0± 5 6 g/L) ,明显高于对照组 (78 0± 6 9g/L和 4 3 0± 6 2 g/L)、(96 0± 7 4 g/L和 5 2 0± 6 9g/L) (P <0 0 5与P <0 0 1)。结论　药物性肝衰大鼠脾内移植微囊化异种肝细胞有显著逆转肝功能和提高生存率的作用。     

兰索拉唑对乙醇诱导大鼠胃黏膜损伤的保护作用及其机制

目的　研究兰索拉唑 (LP)对乙醇诱导大鼠胃黏膜损伤的保护作用 ,探讨胃泌素受体和环氧化酶 2 (COX 2 )表达在此过程中的作用。方法　大鼠ig给予LP 0 5、5、5 0mg·kg-1·d-1,或ig联合给予LP 5 0mg·kg-1·d-1和胃泌素受体拮抗剂AG 0 4 1R 3、10、30mg·kg-1·d-1,对照组ig给予羧甲基纤维素 (CMC) 2 5mg·kg-1·d-1,连续 14d。末次给药后 8h各组大鼠ig给予无水乙醇 1ml,观察胃损伤指数 (LI)及光镜下的胃黏膜病理学改变。酶免疫方法测定胃黏膜前列腺素E2 (PGE2 )水平 ,WesternBlot和免疫组化检测胃黏膜COX 2表达。评价特异性COX 2抑制剂NS 398对LP诱导的PGE2 合成及胃黏膜保护作用的影响。结果　在 0 5、5、5 0mg·kg-1LP组 ,LI分别为 (2 5 3± 0 33) %、(1 84±0 2 9) %和 (0 83± 0 12 ) % ,小于对照组 (3 6 5± 0 19) % (P<0 0 5 ) ;胃黏膜PGE2 含量分别为 (42 7± 32 ) ,(483± 12 1)和 (6 14± 82 ) pg·g-1wwt ,高于对照组 (2 6 6± 81) pg·g-1wwt(P <0 0 5 )。LP剂量依赖性地增加大鼠胃黏膜COX 2表达。然而 ,同时给予AG 0 4 1R阻断了LP诱导的胃黏膜保护作用、COX 2表达和PGE2 合成。NS 398抑制LP诱导的PGE2 合成及胃黏膜保护作用。结论　LP的胃黏膜保护作用与内源性胃泌素激活胃泌素受     

丝裂霉素C在体外和体内对大鼠肝脏CYP2D1/2,CYP2C11和CYP1A2活性的影响

目的研究丝裂霉素C(MMC)在体外和体内对大鼠肝脏CYP2D1/2,CYP2C11和CYP1A2活性的影响。方法用诱导剂和抑制剂分别在体内和体外调节大鼠肝脏P450同工酶活性，并用HPLC检测3种同工酶各自底物的特定代谢产物，以计算同工酶活性。结果在体外, MMC可以使地塞米松诱导的大鼠肝脏微粒体CYP2D1/2,CYP2C11和CYP1A2活性分别抑制(19±6)%(P<0.05),(85±10)％(P<0.01)和(36±6)%(P<0.05)，并使β-萘黄酮诱导的CYP1A2活性降低(58±6)%(P<0.01)。在体内，以20% LD₅₀的剂量连续3 d或6 d腹腔注射MMC 对大鼠肝脏CYP2D1/2，CYP2C11和CYP1A2活性的影响无统计学差异。结论在体外MMC可以抑制大鼠肝微粒体CYP2D1/2，CYP2C11和CYP1A2的活性，但在体内对这3种细胞色素P450同工酶活性的影响无统计学差异。     

抑制NF-κB活性对糖尿病大鼠肾脏TGF-β1 mRNA表达影响

目的　研究抑制核因子 κB(NF κB)活性对糖尿病大鼠肾脏TGF β1mRNA表达影响。 方法　纯种♂Wistar大鼠分为 3组 :A组为正常对照组 (11只 ) ,B组为糖尿病大鼠未干预组 (11只 ) ,C组为糖尿病大鼠PDTC(NF κB活性抑制剂 )干预组 (9只 )。饲养 18wk后取出肾脏 :以电泳迁移率变动分析技术检测肾组织NF κB活性 ,透射电镜检测肾小球基底膜厚度及系膜基质密度 (系膜基质面积 /系膜面积 ) ,RT PCR检测TGF β1mRNA表达。酶免疫分析法检测 2 4h尿白蛋白排泄 (UAE)。结果　肾组织NF κB活性在B组大鼠肾组织 (1 85± 0 5 4× 10 6)显著高于A组 (0 0 7± 0 11×10 6,P <0 0 1) ,C组 (0 2 5± 0 2 5× 10 6)显著低于B组 (P <0 0 1)。B组与A组比较 ,UAE (2 18± 1 98mgvs 0 4 1± 0 4 7mg,P <0 0 1)、肾小球基底膜厚度 (5 31 6± 10 7 6nmvs 312 4±2 5 4nm ,P <0 0 1)及系膜基质密度 (5 6 4 1± 6 78vs 33 95±5 2 2 ,P <0 0 1)均显著增高 ;C组大鼠UAE(0 5 6± 0 72 )mg、肾小球基底膜厚度 (315 8± 2 1 4 )nm及系膜基质密度 (37 97±7 37)均显著低于B组 (均P <0 0 1)。肾组织TGF β1mR NA表达在B组大鼠 (0 5 3± 0 2 0 )显著高于A组 (0 2 6±0 13,P <0 0 1) ,C组 (0 2 9± 0 10 )显?     

剖宫产术后不同镇痛方法效果观察

目的 :观察剖宫产术后患者用不同镇痛方法的效果及副作用。方法 :将 182例患者随机分为两组 :A组硬膜外给予吗啡 5 m g+氟派啶 5 mg+0 .5 %布比卡因 2 5 m L +0 .9%氯化钠至 10 0 m L ,采用 PCA泵装置 ;B组肌肉注射杜冷丁 5 0 m g,每 6 h给药 1次。结果 :两组患者术后 2 4h内睡眠时间分别为 (6 .3± 2 .5 ) h和 (3.1± 1.72 ) h(P<0 .0 1) ,肛门排气时间分别为 (35 .6± 14.3) h和 (4 7.5± 11.6 ) h(P<0 .0 1) ,术后 2 h内产后出血量分别为 (12 5± 6 4) m L和 (196± 78) m L (P<0 .0 1)。结论 :PCA方式镇痛是一种有效的临床术后镇痛方法 ,能减少用药量及副作用 ,提高镇痛效果。     

不同月龄大鼠前列腺组织中一氧化氮水平及其生理意义

目的　探寻前列腺组织中一氧化氮 (NO)水平与年龄之间的关系。方法　应用分光光度法测定 2、6、12月龄各 6只大鼠前列腺组织中的NO水平。结果　 2、6、12月龄大鼠前列腺组织中NO水平分别为 :46 48± 7 16 μmol/L、2 7 2 6± 5 83μmol/L、2 3 83± 10 2 1μmol/L ,随着月龄增长 ,NO水平逐渐下降 ,三者间有显著性差异 (P <0 0 5 )。结论　前列腺组织中NO水平与年龄有关 ,NO水平随着年龄的增长而下降。前列腺组织中L 精氨酸 一氧化氮 环磷酸鸟苷 (L ARG NO cGMP)系统缺陷可能正是老年性良性前列腺增生症 (BPH)的发病原因之一。     

Regulation of blood pressure by D5 dopamine receptors

Dopamine receptors have been identified in a number of organs and tissues, which include the central and peripheral nervous systems, various vascular beds, the heart, the gastrointestinal tract, and the kidney. Dopamine receptors are classified into D1- and D2- like subtypes based on their structure and pharmacology; during conditions of moderate sodium balance, more than 50% of renal sodium excretion is regulated by D1-like receptors. Most of the knowledge on the actions of dopamine has been focused on the D1 dopamine receptor. The D5 dopamine receptor also belongs to the D1- like receptor subfamily. Disruption of the D5 receptor results in hypertension. However, unlike the D1 receptor, the hypertension in D5 receptor null mice is caused by the increased activity of the sympathetic nervous system, apparently due to activation of oxytocin, V1 vasopressin, and non-NMDA receptors in the central nervous system. In this paper, we review the physiological action of D5 receptor on the central and peripheral nervous systems, and discuss the possible mechanisms by which hypertension develops when the D5 receptor function is perturbed.     

Central Bromocriptine‐Induced Tachycardia is Reversed to Bradycardia in Conscious,Deoxycorticosterone Acetate‐Salt Hypertensive Rats

Abstract: A central dopaminergic origin has been demonstrated for the bromocriptine‐induced tachycardia in conscious, normotensive rats. The present study investigated the effect of bromocriptine on heart rate and the principal site of action of this agonist in conscious, deoxycorticosterone acetate‐salt hypertensive rats, in which altered central dopaminergic activity has been previously reported. Intravenous administration of bromocriptine (150 μg/kg) increased heart rate (49±5 beats/min.) in uninephrectomized control rats, while it induced a significant bradycardia (50±6 beats/min.) in deoxycorticosterone acetate‐salt hypertensive rats. In the latter animals, intravenous (500 μg/kg) or intrathecal (40 μg/rat at T₉–T₁₀) pretreatment with domperidone, a selective dopamine D₂ receptor antagonist that does not cross the blood‐brain barrier, reduced partially, but significantly, the bradycardiac responses to bromocriptine (reduction of about 44% and 48% of the maximal effect, respectively). In contrast, the bromocriptine‐induced bradycardia was fully abolished by intravenous pretreatment with metoclopramide (300 μg/kg), a dopamine D₂ receptor antagonist that crosses the blood‐brain barrier, or by combined pretreatment with intravenous and intrathecal domperidone. These results indicate that, in deoxycorticosterone acetate‐salt hypertensive rats, bromocriptine decreases rather than increases heart rate, an effect that is mediated partly through a peripheral D₂ dopaminergic mechanism and partly through stimulation of spinal dopamine D₂ receptors. They further support the concept that, in normotensive, conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at both peripheral and spinal dopamine D₂ receptors.     

Alterations in peripheral and central dopamine receptor sensitivity after subchronic treatment with fluphenazine and sulpiride

The effects of subchronic treatment with the antipsychotic drugs fluphenazine and sulpiride on the sensitivity of peripheral neuronal dopamine receptors and central dopamine autoreceptors were evaluated. The ability of apomorphine, a dopamine agonist, to inhibit electrically induced sympathetic vasoconstriction in pithed rats, and apomorphine-induced inhibition of spontaneous locomotor activity in awake rats were used as indices of peripheral and central dopamine receptor sensitivity, respectively. A single injection of fluphenazine decanoate, a long-acting preparation of fluphenazine, enhanced the central locomotor inhibitory effect of low doses of apomorphine 4 and 6 weeks after drug administration, whereas the antidopaminergic effect on peripheral dopamine receptors was prolonged and persisted at least up to 6 weeks. In another set of experiments rats were treated with fluphenazine hydrochloride and sulpiride for 10 days and subsequently challenged with apomorphine after various withdrawal times. Both antipsychotic drugs augmented the inhibitory effect of apomorphine in the periphery, although the time courses of the potentiation were different. Both treatments also enhanced the locomotor inhibitory effect of apomorphine. These results are in line with our previous finding that long-term treatment with dopamine antagonists can induce neuronal dopamine receptor up-regulation also outside the central nervous system. Peripheral neuronal dopamine receptors thus show similar adaptive responses to long-term blockade as central dopamine autoreceptors, and may serve as a useful experimental model in studies concerned with mechanisms of dopaminergic autoregulation in the central nervous system.     

Dopamine receptor reappearance after irreversible receptor blockade: effect of chronic estradiol treatment of ovariectomized rats.

It is well established that estrogen modulates central dopamine functions; however, the mechanism of this interaction is still poorly understood. We have used peripheral N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) administration to induce irreversible blockade of dopamine receptors in ovariectomized female rats, which were pretreated with estradiol (10 micrograms, twice each day for 2 weeks) or its vehicle, in order to investigate the effect of estradiol on dopamine receptor repopulation kinetics. As previously observed, chronic estradiol treatment increased both striatal D1 and D2 dopamine receptor densities and left affinities unchanged. Anterior pituitary D2 dopamine receptor density remained unchanged. One day after EEDQ administration, a similar decrease (80%) of [3H]SCH 23390 and [3H]spiperone binding to striatum of estradiol- and vehicle-treated animals was observed. Anterior pituitary D2 dopamine receptor specific binding was reduced by about 50% the day after EEDQ. Recovery after EEDQ administration showed that both receptor production rate and degradation rate constants of anterior pituitary D2 and striatal D1 receptors were slowed after chronic estradiol treatment, whereas recovery rates for striatal D2 dopamine receptors were unaffected. EEDQ administration in vehicle-treated rats did not significantly affect plasma prolactin levels, whereas the combination of estradiol pretreatment and EEDQ administration led to increased plasma prolactin levels, compared with estradiol-treated animals that did not receive EEDQ. This suggests that only a fraction of anterior pituitary dopamine receptors are required for a maximal inhibition of prolactin secretion. Estradiol affected both striatal D1 and D2 dopamine receptor densities but only D1 dopamine receptor repopulation kinetics, suggesting that it may act by different mechanisms on each dopamine receptor. Alternatively, estradiol may affect dopamine receptor interaction. Thus, the present study raises the possibility that a biochemical D1/D2 receptor interaction affects dopamine receptor biosynthesis, turnover, and/or gene expression and that estradiol may influence this dopamine receptor interaction in the striatum.     

2型糖尿病大鼠膀胱M_3受体改变的实验研究

目的研究病程3周的2型糖尿病大鼠膀胱M3受体含量及其基因转录水平的变化情况,探讨糖尿病性膀胱早期发病机制中逼尿肌M3受体的改变情况。方法2 d龄雌性Wistar大鼠随机分成2型糖尿病组和正常对照组,链脲佐菌素按90 mg/kg体重腹腔注射并结合高糖高脂饮食诱导2型糖尿病大鼠模型。于糖尿病病程3周时进行下列实验:反转录-聚合酶链反应(RT-PCR)方法检测M3受体mRNA的含量;Western blotting方法检测膀胱M3受体蛋白的含量。结果RT-PCR方法检测结果显示:糖尿病组大鼠膀胱M3受体mRNA的数量显著高于正常对照组[(52.0±5.7)%vs(35.6±11.7)%,P<0.05]。Western blotting方法检测结果显示:糠尿病组大鼠膀胱M3受体含量显著高于正常对照组[(30.9±2.1)%vs(23.4±4.7)%,P<0.01]。结论本研究证实了糖尿病性膀胱早期M3受体的生物合成上调这一改变,从而解释了糖尿病早期膀胱逼尿肌收缩力增加这一现象。这可能是早期糖尿病性膀胱病变的一个发病机制。     

Sulpiride isomers exhibit reversed stereospecificity for D-1 and D-2 dopamine receptors in the CNS

We have investigated the stereospecificity of the interaction of (?) and (+)sulpiride with [³H]cis-flupentixol and [³H]spiperone binding to D-1 and D-2 dopamine receptors respectively in rat strialum. Both isomers of sulpiride compete more potently at D-2 vs. D-1 dopamine receptors. (?)Sulpiride is 50-fold more potent than (+)sulpiride in blocking D-2 receptors, while (+)sulpiride is 3-fold more potent than (?)sulpiride at D-1 receptors. This reversed stereospecificity of sulpiride interactions with CNS D-1 and D-2 dopamine receptors is similar to the stereospecificity of sulpiride interactions at DA₁ and DA₂ dopamine receptors in peripheral vascular beds.Biochemical and radioligand binding studies indicate the presence of D-1 and D-2 dopamine receptor subtypes in the central nervous system (CNS) (Creese, Sibley, Hamblin and Leff, 1983). Pharmacological studies suggest that a similar subclassiflcation may be made for dopamine receptors found in peripheral vascular beds based on their postsynaptic (DA₁) or presynaptic (DA₂) localization (for review see Goldberg and Kohli, 1982). Some pharmacological data suggest that similarities may exist between D-1 vs. DA₁ and D-2 vs. DA dopamine receptor subtypes (Goldberg and Kohli, 1982; Creese, 1983; Shepperson, Duval, Massingham and Langer, 1982; Schmidt and Imbs, 1980). Interestingly, all investigations indicate that DA₁ and DA₂ receptors show an opposite stereoselectivity for the (?)(S) and (+)(R) stereoisomers of sulpiride whereby DA₂ receptors are more potently blocked by (?)sulpiride vs. (+)sulpiride and DA₁ receptors are slightly more sensitive to (+)sulpiride vs. (?)sulpiride. The present study reports a similar stereoselectivity for CNS D-2 and D-1 dopamine receptors, respectively, measured by radioligand binding techniques.     

Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats

Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.     

Adrenergic receptor blocking agents: Effects on central noradrenaline and dopamine receptors and on motor activity

Phenoxybenzamine, but not phentolamine or propranolol, blocked central noradrenaline receptors in flexor reflex experiments on the rat spinal cord using the selective noradrenaline receptor stimulating agent clonidine. None of these three drugs blocked dopamine receptors in experiments on turning of unilaterally striatectomized rats induced by the dopamine receptor stimulating agent apomorphine. The -methyltyrosine-induced disappearance of noradrenaline in the central nervous system of rats and mice was accelerated by phenoxybenzamine at doses related to the functional changes, whereas the other drugs were inefficient. The disappearance of dopamine was decelerated by phenoxybenzamine, but not by phentolamine or propranolol.The effects of the adrenergic receptor blocking agents on motor activity were studied in a model in which clonidine potentiated the activation induced by apomorphine in reserpine-treated mice. Phentolamine (20 mg/kg) and propranolol (10 mg/kg) reduced the stimulation seen both after apomorphine alone and in combination with clonidine, indicating nonspecific sedative effects. Phentolamine (10 mg/kg) blocked the peripheral effects of clonidine but did not markedly diminish the activation induced by the receptor stimulants. Phenoxybenzamine (20 mg/kg) blocked the clonidine-induced potentiation without interfering with the apomorphine-induced stimulation and can thus be used as a blocking agent of central and peripheral noradrenaline receptors in behavioural experiments.     

Protection of the right ventricle from ischemia and reperfusion by preceding hypoxia

We have previously shown that 2 weeks of hypoxia protect the right ventricle of the rat heart from subsequent ischemia and reperfusion (I/R). In the present study, we examined the following: (1) Do shorter periods of hypoxia protect from subsequent I/R? (2) Does intermittent normoxia increase the cardioprotective effect? (3) Is hypoxia-inducible factor-1α (HIF-1α), erythropoietin (EPO), or vascular endothelial growth factor (VEGF) involved in the protective effects? Preischemic cardiac work was followed by global ischemia, reperfusion, and postischemic cardiac work (15 min each). External heart work was determined at the end of both work phases. Four groups of hearts were investigated: hearts from normoxic rats (n?=?8), hearts from rats after 24 h of continuous hypoxia (10.5% inspired oxygen, n?=?7), hearts from rats after 24 h hypoxia with a single intermission of 30 min normoxia (n?=?9), and hearts from rats after 24 h hypoxia and multiple intermissions of 30 min normoxia (n?=?7). Protein levels of HIF-1α and mRNA levels of EPO and VEGF were determined in right ventricular tissue of normoxic and hypoxic hearts. Postischemic right heart recovery was better in all three hypoxic groups compared with normoxic hearts (61.8?±?5.9%, 65.6?±?3.0%, and 75.7?±?2.6% vs. 46.0?±?3.9%, p?p?p?=?0.02). No differences in EPO and VEGF mRNA levels were found between normoxic and hypoxic hearts. Twenty-four hours of continuous hypoxia protect the isolated working right heart from subsequent ischemia and reperfusion. When preceding hypoxia is interrupted by multiple reoxygenation periods, there is a further significant increase in cardiac functional recovery. HIF-1α may be involved in the protective effect.