PKC和ROCK对硝苯地平舒张血管作用的影响

目的:探讨蛋白激酶C(PKC)及Rho相关激酶(ROCK)对硝苯地平舒张大鼠离体胸主动脉血管环作用的影响。方法:采用离体血管环灌流装置观察硝苯地平对基础状态血管环及去甲肾上腺素(NE,10~(-6)mol/L)或KCl(60mmol/L)预收缩血管环的张力变化,并利用PKC抑制剂和ROCK抑制剂等工具药观察对硝苯地平舒血管作用的影响并探讨可能机制。结果:系列浓度硝苯地平对基础状态血管环张力无明显影响,对NE和KCl预收缩的血管环具有浓度依赖性舒张作用(P 0. 05),去内皮组舒张作用与内皮完整组比较无明显差异。预孵PKC抑制剂星孢菌素(STA,10~(-8)mol/L)及激动剂佛波酯(PMA,10~(-7)mol/L)后,STA能增强硝苯地平对血管的舒张作用,而PMA能减弱硝苯地平对血管的舒张作用(P 0. 05);预孵ROCK抑制剂法舒地尔(fasudil,10~(-6)mol/L)及激动剂血管紧张素Ⅱ(Ang-Ⅱ,10-9mol/L)后,fasudil能增强硝苯地平对血管的舒张作用,而Ang-Ⅱ能减弱硝苯地平对血管的舒张作用(P 0. 05);钾通道阻滞剂BaCl_2(10~(-4)mol/L)、四乙胺(10~(-3)mol/L)、格列本脲(10~(-5)mol/L)和4-氨基吡啶(10~(-3)mol/L)对硝苯地平的舒张血管作用无明显影响。在无钙且含高浓度KCl的溶液中,硝苯地平可浓度依赖性地抑制累积浓度的CaCl_2对大鼠离体主动脉环的收缩作用(P 0. 05)。在无钙液中,硝苯地平对NE所引起的收缩无明显影响。结论:硝苯地平能够呈浓度依赖性地舒张大鼠主动脉,其舒张血管作用为非内皮依赖性,且与抑制细胞外钙内流密切相关,其舒张血管作用部分与抑制PKC和ROCK作用相关。     

槲皮素改善高糖损伤大鼠冠脉肌原性反应的机制研究

目的:通过大鼠冠状动脉(coronary artery,CA)张力测定和全细胞膜片钳记录CA血管平滑肌细胞(vascular smooth muscle cells,VSMC)的电压门控性钾通道(voltage-gated K~+channel,Kv)电流,研究槲皮素改善高糖损伤大鼠CA肌原性反应的机制。方法:从正常SD大鼠急性分离得到CA环,然后分成6组:(1)正常对照组;(2)高糖组;(3)高糖+低剂量(3μmol/L)槲皮素组;(4)高糖+中剂量(10μmol/L)槲皮素组;(5)高糖+高剂量(30μmol/L)槲皮素组;(6)高糖+蛋白激酶C(protein kinase C,PKC)抑制剂C6303+高剂量槲皮素组。利用血管张力测定,检测CA环对血管收缩剂(60 mmol/L KCl和0.1 mmol/L U46619)的反应,并将CA环用60 mmol/L KCl预收缩后,用乙酰胆碱(acetylcholine,ACh;10~(-9)~10~(-5)mol/L)进行舒张,计算ACh引起CA环张力下降幅度与预先收缩的百分比。急性分离得到大鼠CA的VSMC,然后记录Kv电流。结果:与正常対照组相比,高糖组CA环对60mmol/L KCl和0.1 mmol/L U46619的反应明显升高;中、高剂量槲皮素的干预可以使高糖所致CA环对血管收缩剂的反应降低,孵育PKC特异性抑制剂C6303可减弱槲皮素的作用。与正常对照组相比,高糖组大鼠离体CA环对ACh的舒张幅度明显减弱。槲皮素的干预可以改善高糖孵育的大鼠离体CA环对ACh的舒张反应,C6303可以减弱槲皮素的作用。高糖孵育明显抑制CA VSMC的Kv电流,槲皮素干预可以减弱高糖对CA VSMC Kv电流的影响,孵育C6303可减弱槲皮素的作用。结论:槲皮素对高糖损伤大鼠CA肌原性反应具有保护作用,该作用与增大VSMC的Kv电流和激活PKC有关。     

Zacopride增强心肌内向整流钾电流(IK1)效应的受体和信号转导通路

目的:探讨5-HT4受体激动剂兼5-HT3受体阻断剂zacopride增强心肌内向整流钾电流(IK1)效应的受体和细胞信号转导机制.方法:应用全细胞膜片钳技术记录大鼠心室肌细胞膜IK1电流,分别观察10 μmol/L 5-HT4受体阻断剂 RS23597-190、10 μmol/L 5-HT3受体激动剂间氯苯双胍(m-CPBG)、5 μmol/L PKA 抑制剂 KT5720、5 μmol/L PKC 抑制剂GF109203x 和 5 μmol/L PKG抑制剂 KT5823对zacopride 增强IK1的影响.结果:10 μmol/L 5-HT4受体阻断剂RS23597-190本身可抑制IK1电流,在预先应用RS23597-190的基础上,1 μmol/L zacopride仍可明显激动IK1通道,使其内向电流(-100 mV)增强32.5% (P< 0.05).10 μmol/L 5-HT3受体激动剂m-CPBG对IK1电流无明显影响,也不能逆转1 μmol/L zacopride对IK1的增强效应(P> 0.05).此外,5 μmol/L PKA 阻断剂 KT5720能显著抑制1 μmol/L zacopride对IK1的增强效应(P< 0.05),而PKC 阻断剂GF109203x和PKG阻断剂KT5823则对1 μmol/L zacopride的效应无明显影响(P> 0.05).结论:Zacopride对 IK1的增强作用可能经由PKA介导的信号转导通路,而不依赖于5-HT3和5-HT4受体.     

姜黄素通过HO/GC途径对抗高糖诱导的血管收缩功能下降

目的:研究姜黄素是否可对抗高糖诱导的血管收缩功能下降,并探讨其作用机制。方法:采用血管环离体灌流装置,观察SD大鼠胸主动脉环的收缩反应;测定主动脉胆红素生成量反映血红素加氧酶-1(HO-1)的活性。结果:(1)与空白对照组(含11mmol/L葡萄糖)相比,经44mmol/L葡萄糖(高糖)孵育血管4h后,主动脉环对苯肾上腺素(PE)引起的血管收缩反应下降;(2)姜黄素(3×10-11-3×10-10mol/L)与高糖联合孵育,均能不同程度地抑制高糖诱导的血管PE收缩反应的下降;(3)姜黄素孵育后可引起血管HO活性增高;HO-1抑制剂锌原卟啉Ⅸ(ZnPP)可完全取消姜黄素的抗高糖损伤作用;(4)鸟苷酸环化酶(GC)抑制剂亚甲蓝可部分阻断姜黄素的保护作用。结论:姜黄素可能通过诱导HO-1活性增加和激活GC途径对抗高糖引起的血管收缩功能降低。     

辛夷二氯甲烷提取物对离体大鼠胸主动脉环的舒张作用及其机制

目的:研究辛夷二氯甲烷提取物(CEF)的舒张血管作用以及其作用机制。方法:采用大鼠离体血管功能实验装置,描记张力变化,每组血管来自5只同批大鼠,分别保留和去除内皮。结果:CEF(0.1-1000mg/L)对去氧肾上腺素(PE)预收缩的血管环具有浓度依赖的舒张作用,内皮去除前后最大舒张效率Emax分别为78.68%±6.03%和64.98%±13.90%,该舒张作用为非内皮依赖性(P0.05)。钾通道阻断剂格列苯脲(Glib,10μmol/L)、四乙基氯化铵(TEA,3mmol/L)、氯化钡(BaCl2,100μmol/L)和鸟苷酸环化酶抑制剂1H-[1,2,3]恶二唑[4,3-a]喹喔啉-1-酮(ODQ,10μmol/L)预处理不能抑制CEF对去除内皮血管的舒张效应;CEF对血管紧张素Ⅱ(AngⅡ)、前列腺素F2α(PGF2α)、多巴胺(Dopa)、血管加压素(Vaso)、五羟色胺(5-HT)和PE诱发的血管收缩均具有明显的抑制作用(P0.01),抑制率分别为91.31%、82.11%、95.32%、90.53%、72.22%和83.63%。CEF对无钙液中PE引起的内钙释放和无钙高钾液中Ca2+收缩曲线均有显著的抑制作用(P0.01)。结论:CEF具有舒张血管作用,其机制可能与抑制外钙内流和胞质内钙释放干扰胞质内钙离子平衡有关。     

一氧化氮合酶抑制物对大鼠离体乳头肌收缩力的影响及其机制

目的:探讨一氧化氮合酶(NOS)抑制物对电刺激大鼠离体左心室乳头肌收缩力的影响及其机制。方法:制备大鼠离体左心室乳头肌条,用Muscle Research System记录电刺激(频率1 Hz、波宽5 ms)诱导心肌收缩张力。结果:与正常对照组比较,用30μmol/L内源性NOS抑制物非对称二甲基精氨酸(asymmetric dimethylarginine,ADMA)孵育乳头肌60 min后,肌条对电刺激收缩张力明显降低;用相同浓度的外源性NOS抑制物NG-硝基-L-精氨酸孵育60 min,均可产生与ADMA相似的抑制作用。用1 mmol/L一氧化氮(NO)合成前体L-精氨酸或10μmol/L NO供体硝普钠预孵育肌条15 min,再与ADMA共孵育60 min,均可逆转ADMA对心肌收缩的抑制作用。用10μmol/L蛋白激酶C抑制剂chelerythrine或抗氧化剂N-乙酰半胱氨酸预处理,亦可逆转ADMA的抑制作用。结论:NOS抑制物对电刺激大鼠离体左心室乳头肌收缩具有抑制作用,可能是由于减少NO生成、活化蛋白激酶C、使氧化应激增加所致。     

PKC信号通道对严重创伤性休克大鼠血管舒缩功能的调节作用

目的探讨蛋白激酶C(PKC)信号通道是否参与了严重创伤性休克后血管舒缩功能的调控。方法取严重创伤性失血性休克大鼠的腹腔动脉(CA),观察PKC激活剂PMA及PKC抑制剂Staurosporine对休克后去甲肾上腺素(NE)、氯化钾(KC l)诱导的血管收缩反应的影响,以及PMA对乙酰胆碱(ACh)介导的内皮依赖性舒张(EDR)和硝普钠(SNP)介导的内皮非依赖性舒张(EIDR)反应的影响。结果严重创伤性失血性休克大鼠腹腔动脉对NE、KC l诱导的收缩反应以及ACh、SNP介导的舒张反应都显著降低;PMA(0.01、0.1、1μmol/L)对NE、KC l诱导的休克血管收缩反应有显著的增强作用,且呈浓度依赖性;Staurosporine(100 nmol/L)可使休克血管对NE、KC l的反应性进一步降低,同时Staurosporine预处理能显著抑制PMA增强休克血管收缩反应的作用;PMA(0.1μmol/L)可使ACh和SNP诱导的舒张反应都进一步降低。结论PKC信号通道对严重创伤后的血管舒缩功能具有重要的调节作用。     

平滑肌BKCa通道在运动改变大鼠胸主动脉舒缩特性中的作用

背景：大电导钙激活钾通道(BK_Ca)是调节细胞兴奋性和血管张力的重要离子通道,有关大动脉平滑肌BK_Ca通道的作用机制鲜有报道。 目的：观察有氧运动对大鼠胸主动脉舒缩特性的影响,并探讨平滑肌BK_Ca通道在其中的作用。 方法：将20只Wistar大鼠随机分为安静对照组和有氧运动组,运动组进行12周跑台运动,坡度0°, 20 m/min, 60 min/d, 5 d/周。之后每组5只大鼠行股动静脉插管术。恢复1 d后,于在体、清醒状态下进行心血管功能监测。另各组5只大鼠,取胸主动脉制备去内皮血管环,进行体外血管收缩特性检测。 结果与结论：①有氧运动后静脉注射去甲肾上腺素引起的升压反应幅度下降。②静脉注射BK_Ca通道阻断剂Iberiotoxin可诱发升压反应,且运动组更显著。③ 120 mmol/L KCl在两组胸主动脉血管环均可诱发收缩,最大张力差异无显著性意义。④去甲肾上腺素(10^-9~10^-5 mol/L)诱发的血管收缩呈浓度依赖性,但运动组的最大张力显著低于安静组。⑤Iberiotoxin (3×10^-8 mol/L)预处理血管后,可增强去甲肾上腺素(10^-5 mol/L)诱发的张力增加,且运动组增加幅度显著大于安静组。⑥BKCa通道开放剂NS1619 (10^-10~10^-6 mol/L)可引起去甲肾上腺素诱发的血管收缩张力下降,且运动组对其敏感性(pD2)增加。提示,有氧运动可诱导大鼠心血管反应性和胸主动脉舒缩特性改变,其中平滑肌BKCa通道起着重要作用。     

ERK1/2及JNK参与DL0805抑制血管紧张素Ⅱ引起的大鼠离体胸主动脉环收缩

目的研究Rho激酶抑制剂DL0805对血管紧张素Ⅱ(AngⅡ)引起的大鼠离体胸主动脉环收缩反应的影响及其可能的机制。方法测定离体血管张力观察大鼠胸主动脉环收缩反应,Western blot检测大鼠离体胸主动脉环ERK1/2和JNK蛋白磷酸化,和AngⅡ1型受体(AT1R)蛋白表达水平。结果 DL0805(10、25和50μmol/L)浓度依赖性地抑制AngⅡ(100 nmol/L)引起的内皮完整或去内皮的大鼠离体胸主动脉环收缩(P<0.01,P<0.001),DL0805(25和50μmol/L)抑制AngⅡ(100 nmol/L)诱导的ERK1/2和JNK的活化(P<0.05,P<0.01和P<0.001),但DL0805(5、25和50μmol/L)对AngⅡ刺激的血管环AT1R蛋白表达水平无显著影响。结论 DL0805抑制AngⅡ引起的大鼠离体胸主动脉环收缩,其机制可能与其抑制AngⅡ诱导的ERK1/2和JNK活化有关。     

高钾溶液对猪冠状动脉内皮细胞功能影响的实验研究

目的 :探讨高钾溶液对猪冠状动脉内皮细胞功能的影响及其机制。方法 :取新鲜猪心外膜下冠状动脉前降支下三分之一 ,切成 3mm长的血管环。采用器官槽法 ,分别用Krebs Henseleit重碳酸盐缓冲液 (KH)、2 0mmol/L的高钾溶液、50mmol/L的高钾溶液浸泡血管环 1h后 ,检测在 7μmol/L环加氧酶阻断剂消炎痛、3 0 0 μmol/L一氧化氮合成酶阻断剂N 硝基 L 精氨酸、1mmol/L钙激动性钾通道阻断剂四乙胺、或 3μmol/LATP敏感性钾通道阻断剂优降糖的作用下 ,3 0nmol/L前列腺素F2α引发的预收缩强度和非受体介导钙离子载体 ( 10 -1 0 ～ 10 -6mol/L)引发的内皮源性舒张反应。结果 :与单纯浸泡于KH的冠状动脉相比 ,内皮源性超极化因子 (EDHF)介导的内皮源性舒张反应 ,经 2 0mmol/L、50mmol/L高钾溶液及四乙胺作用后显著降低 ,但加入优降糖后改变不明显。结论 :EDHF在冠状动脉内皮源性舒张中起重要的作用 ,高浓度钾离子抑制EDHF的作用、EDHF介导血管舒张的作用过程主要与钙激动性钾通道有关     

酸中毒致大鼠离体冠状动脉收缩的机制

目的:探讨细胞外酸中毒(pH_(ex)6.8)致大鼠离体冠状动脉(RCA)收缩的机制。方法:采用离体微血管张力法,通过观察Na~+-H~+交换体1(NHE-1)选择性抑制剂cariporide(HOE-642)或Na~+-HCO_3~-共同转运体(NBC)抑制剂S0859预孵对pH_(ex)6.8所致RCA收缩的影响,探讨酸碱转运体在酸中毒收缩RCA中的作用;通过观察氯通道抑制剂NPPB和尼氟酸(NFA)预孵及细胞外去除氯离子对pH_(ex)6.8所致RCA收缩的影响,探讨氯离子通道在酸中毒收缩RCA中的作用。结果:pH_(ex)6.8引起RCA静息张力升高,最大张力为(3.90±0.95)mN。30μmol/L HOE-642和100μmol/L S0859均抑制pH_(ex)6.8引起的RCA收缩(P0.01)。NPPB和NFA均呈浓度依赖性地抑制pH_(ex)6.8引起的RCA收缩和KCl(60 mmol/L)引起的收缩。100μmol/L的NPPB和NFA均抑制U46619(1μmol/L)引起的RCA收缩(P0.01)。等摩尔NaBr代替细胞外液中NaCl后,几乎完全抑制pH_(ex)6.8引起的RCA收缩(P0.01),但是对KCl(60 mmol/L)或U46619(1μmol/L)引起的RCA收缩无显著影响。结论:细胞外液酸化所致的RCA收缩与激活NHE-1和NBC及促进氯离子跨细胞膜运动有关。     

5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats

Numerous studies support a role for the endogenous 5-hydroxytryptamine (5-HT) system in the hypothermic effect of capsaicin. None of those studies, however, selectively delineate a role for 5-HT reuptake or 5-HT receptors in this regard. In the present investigation, we determined if the blockade of 5-HT reuptake or the activation of 5-HT_1A or 5-HT₂ receptors modulates capsaicin-evoked hypothermia. The administration of capsaicin (0.2–1 mg/kg, i.m.) produced dose-related hypothermia. Fluoxetine (10 mg/kg, i.p.), a selective serotonin reuptake inhibitor (SSRI), did not affect body temperature. For combined administration, pretreatment with fluoxetine (10 mg/kg, i.p.) significantly attenuated the hypothermia caused by capsaicin (0.5 and 1 mg/kg, i.m.). For the 5-HT receptor experiments, we pretreated rats with either WAY 100635, a 5-HT_1A receptor antagonist, or mianserin, a 5-HT₂ receptor antagonist, and then administered a fixed, hypothermic dose of capsaicin (1 mg/kg, i.m.). WAY 100635 (1 mg/kg, s.c.) administration did not affect capsaicin-evoked hypothermia. This indicates that 5-HT_1A receptor activation does not play a major role in the hypothermic effect of capsaicin. In contrast, pretreatment with mianserin (10 mg/kg, i.p.) enhanced the hypothermic effect of capsaicin (1 mg/kg, i.m.). The present data reveal that capsaicin-evoked hypothermia in rats is attenuated by the blockade of 5-HT reuptake and enhanced by the antagonism of 5-HT₂ receptors.     

Muramyl dipeptide (MDP) and 5-HT receptors. Neuroimmunomodulatory effects of MDP are probably not mediated through 5-HT4 or 5-HT1A receptors

A possible interaction of immunomodulator muramyl dipeptide (MDP) with 5-HT₄ and 5-HT_1A receptors was investigated. The activation of 5-HT₄ receptors releases acetylcholine from nerve terminals, thereby contracting the guinea-pig distal ileum. The whole ileum segments were therefore cut and placed into the bath. The preparations were contracted by 5-HT (10 nM-3.2 µM); these contractions were totally abolished in the presence of atropine (1 µM) and significantly attenuated in the presence of SDZ-205,557 (320 nM). The 5-HT evoked contractions remained unchanged in the presence of MDP (5, 50 or 500 nM). MDP (10 nM-3.2 µM) could not directly contract the preparations. In further experiments, the possible interaction of MDP with 5-HT_1A receptors was investigated. The activation of 5-HT_1A receptors inhibits the release of acetylcholine from nerve terminals, thereby decreasing the height of electrically evoked neurogenic twitches of guinea-pig ileum. The whole ileum segments were cut, placed into the bath and stimulated electrically. Selective 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) decreased the height of twitches and this effect was significantly attenuated in the presence of 5-HT antagonist metergoline (1 µM). The effect of 8-OH-DPAT remained unchanged in the presence of MDP (5, 50 or 500 nM). MDP (10 nM-3.2 µM) did not exert any direct effect on the preparations. These results suggest that MDP interacts with neither 5-HT₄ nor 5-HT_1A receptors.     

Characterization of a neuronal interleukin-1 receptor and the corresponding mRNA in the mouse anterior pituitary cell line AtT-20.

The serotonin (5-HT)_1A agonist, LY 165,163 (1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine), also known as PAPP, has been suggested to exert effects via an interaction with dopamine receptors. Thus, in this study, we examined its ability to induce rotation in rats sustaining unilateral 6-hydroxy-dopamine lesions of the substantia nigra, an in vivo model of dopaminergic activity. In analogy to the direct dopamine (mixed D₁/D₂) agonist, apomorphine, (0.01–0.63 mg/kg), LY 165,163 (0.16–10.0 mg/kg) dose-dependently elicited robust and substained contralateral rotation. Its maximal effect was comparable to that of apomorphine and its duration of action more extended. Rotation elicited by LY 165,163 (10.0 mg/kg) was resistant to the 5-HT_1A antagonist, (−)-alprenolol. It was also unaffected by the selective D₁ antagonist, SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5,tetraphydro-1H-3- benzazepine) (2.5 mg/kg) or the selective D₂ antagonist, raclopride (10.0 mg/kg) when each was administered alone. However, upon joint administration they clearly diminished the effect of LY 165,163. The dopamine antagonist, haloperidol (D₂ > D₁) also reduced the action of LY 165,163. This profile of partial antagonism by mixed D₁ and D₂ receptor blockade has been reported previously for apomorphine and contrasts to that seen with selective D₁ or D₂ agonists, the actions of which are completely blocked by D₁ or D₂ antagonists, respectively. In conclusion, the present data demonstrate that LY 165,163 exerts pronounced rotation in nigral-lesioned rats: this reflects a mixed D₁/D₂ action rather than an activation of 5-HT_1A sites. Thus, in addition to an agonist action at 5-HT_1A receptors, dopaminergic effects contribute to the pharmacological profile of LY 165,163.     

Progestins used in hormonal replacement therapy display different effects in coronary arteries from New Zealand white rabbits

Objectives: The aim of this study was in an animal model to assess the vascular effects of different progestins commonly used in hormonal replacement treatment. Methods: Fifty-six non-atherosclerotic, ovariectomized New Zealand white rabbits were randomized into seven groups: (1) medroxyprogesterone acetate (MPA), (2) norethisterone acetate (NETA), (3) conjugated equine estrogens (CEE), (4) 17-β-estradiol (E2), (5) MPA+CEE, (6) NETA+E2, (7) or placebo (n=8) and given hormonal treatment through the diet for 4 weeks. Ring segments from the left proximal coronary artery and from the distal part of the left anterior descending coronary artery were microdissected and mounted for isometric tension recordings in a myograph. The vasoconstrictory responses induced by potassium, endothelin-1, calcium and N_w-nitro- -arginine methyl ester, and the vasodilatory response induced by acetylcholine and sodiumnitroprusside were investigated. The maximum contraction/relaxation (E_max) and the concentration required to induce half the maximum response (EC₅₀) were determined. EC₅₀ values were expressed as the negative logarithm to the molar concentration, pD₂=−log EC₅₀. Results: Treatment with MPA alone caused when compared to treatment with NETA an increase in tension development in the distal coronary artery after the addition of potassium (6.36±0.36 versus 4.31±0.42 P<0.005) (single dose response, mN/mm, mean±S.E.M.) and endothelin-1 (9.41±0.82 versus 6.43±0.73 P<0.05) (E_max, mN/mm, mean±S.E.M.). Treatment with MPA compared to placebo caused an endothelin-1 induced increase of E_max in the distal coronary artery (9.21±0.87 versus 6.51± 0.65 P<0.05) and a calcium induced increase of pD₂ in both coronary arteries (2.98±0.19 versus 2.42±0.12 P<0.05, proximal coronary artery) (3.26±0.09 versus 2.9±0.1 P<0.05, distal coronary artery) (pD₂, mean±S.E.M.). Treatment with NETA compared to placebo in the proximal coronary artery, after the addition of sodiumnitroprusside caused a decrease of pD₂ (5.33±0.19 versus 5.94±0.13 P<0.05). Treatment with E2 compared to treatment with CEE in the proximal coronary artery caused a decrease of pD₂ after the addition of sodiumnitroprusside (5.00±0.16 versus 5.77±0.28 P<0.05). No significant differences were found between MPA+CEE and NETA+E2. Conclusion: Treatment with MPA alone seems to enhance the contractile response to potassium and endothelin-1 in the distal coronary artery compared to NETA, indicating that different progestins used in hormonal replacement treatment may display different effects on contractile functions of coronary arteries.     

Periodic abstinence enhances nociception without significantly altering the antinociceptive efficacy of spinal morphine in the rat

Affective disorders are more common in women. The forced swim test acts like a depressive stimulus. Hippocampus and frontal cortex 5-HT_1A receptors of female and male Wistar rats subjected to the forced swim test were compared with a sham group. The forced swim test diminishes (P<0.05) the hippocampus ³H-8OH-DPAT bound in the female rats (184±16 fmol/mg protein) with respect to the male rats (309±41 fmol/mg protein) and to the female sham rats (255±20 fmol/mg protein). The forced swim test increases the frontal cortex 5-HT_1A receptors in the female rats with respect to the female sham group (40.4±5 versus 24.7±4 fmol/mg protein, P<0.05). An increased sensibility of the 5-HT_1A receptors to depressive-stimulus may be one mechanism underlying the higher prevalence of depression in female.     

Expression of serotonin2A receptors in Purkinje cells of the developing rat cerebellum

Previous physiological and pharmacological studies have shown that the serotonin_2A (5-HT_2A) receptor is involved in cerebellar functions. However, the expression of 5-HT_2A receptors in the developing cerebellum has not been elucidated to date. In the present immunohistochemical study, we examined developmental changes of the distribution of 5-HT_2A receptors in Purkinje cells of the rat cerebellum from embryonic day 18 (E18) to postnatal day 21 (P21). The weak immunoreaction to 5-HT_2A receptors was found in the deep cerebellar nuclei on E19. In the cerebellar cortex of the hemisphere and the posterior vermis, somata of Purkinje cells became weakly immunoreactive on P0. With the dendritic elongation and arborization, the immunoreaction appeared in the proximal parts of Purkinje cell dendrites. Distal parts of the dendrites became immunoreactive after P12, and were strongly immunolabeled by P21. The present study may provide a structural basis to investigate the roles of 5-HT_2A receptors during the cerebellar development.