血管内皮对狗离体冠状动脉β肾上腺素受体激动剂反应性的影响(英文)

目的:研究内皮细胞对离体冠状动脉β肾上腺素受体激动剂反应性的影响.方法:狗冠状动脉环离体实验,生理记录仪记录血管张力.结果:去甲肾上腺素(NE)和异丙肾上腺素(Iso)引起离体狗冠状动脉剂量依赖性舒张反应,酚妥拉明加强NE的作用.血管去内皮后,对NE和Iso的反应减弱,一氧化氮(NO)合成酶抑制剂N~ω-硝基左旋精氨酸甲酯亦可减弱NE和Iso的作用.结论:β肾上腺素受体激动剂对狗冠状动脉舒张作用部分依赖于内皮.此作用由NO介导.     

三七总皂甙对Sprague-Dawley种系大鼠脑循环的影响

研究三七总皂甙(PNS)对麻醉Sprague-Dawley(SD)大鼠脑循环的影响,并与维拉帕米(Ver)和去甲肾上腺素(NE)进行比较。用电磁流量计测定脑血流量(CBF),以股动脉平均血压(MBP)除以CBF为脑血管阻力(CVR),结果为:PNS50～200mg·kg^-1iv使大鼠的MBP和CVR分别下降14～21%和8～22%,Ver30ug·kg^-1iv表现出类似效应,而NE30ug·kg^-1iv则表现出相反效应,对CBF,PNS100和200mg·kg^-1使其分别减少15±11%和33±10%,而Ver和NE均对其无影响。表明PNS虽具扩张SD大鼠脑血管的作用,但并不因此而增加SD大鼠的脑血流量。     

三七总皂甙对Sprague-Dawley种系大鼠脑循环的影响

研究三七总皂甙（ＰＮＳ）对麻醉Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ（ＳＤ）大鼠脑循环的影响,并与维拉帕米（Ｖｅｒ）和去甲肾上腺素（ＮＥ）进行比较。用电磁流量计测定脑血流量（ＣＢＦ）,以股动脉平均血压（ＭＢＰ）除以ＣＢＦ为脑血管阻力（ＣＶＲ）,结果为：ＰＮＳ５０～２００ｍｇ·ｋｇ－１　ｉｖ使大鼠的ＭＢＰ和ＣＶＲ分别下降１４～２１％和８～２２％,Ｖｅｒ３０ｕｇ·ｋｇ－１ｉｖ表现出类似效应,而ＮＥ３０ｕｇ·ｋｇ－１　ｉｖ则表现出相反效应,对ＣＢＦ,ＰＮＳ１００和２００ｍｇ·ｋｇ－１使其分别减少１５±１１％和３３±１０％,而Ｖｅｒ和ＮＥ均对其无影响。表明ＰＮＳ虽具扩张ＳＤ大鼠脑血管的作用,但并不因此而增加ＳＤ大鼠的脑血流量。     

侧脑室注射apelin-13对大鼠远端结肠推进的影响及机制研究

目的探讨侧脑室apelin-13对大鼠远端结肠推进活动的影响及其作用机制。方法将SD大鼠随机分为6组,每组8只,生理盐水为对照组(i.c.v.,2μL)、apelin-13组(0.1、0.3、1、3、10 nmol,i.c.v.,2μL),通过排珠实验检测各个剂量的apelin-13对大鼠远端结肠推进活动的影响;对照组(3组)分别为大鼠腹腔1次性注射2 m L的M型胆碱能受体的阻断剂阿托品(atropine,ATR)(20mg/kg)组、肾上腺素受体阻断剂酚妥拉明(phentolamine,PHE)(1 mg/kg)和普洛奈尔(propranolol,PRO)(1 mg/kg)组、N型胆碱能受体的阻断剂六烃季铵(hexamethonium,HEX)(1 mg/kg)组;20 min后在对照组基础上,各组分别侧脑室注射2μL 1 nmol apelin-13,考察apelin-13在结肠推进作用上的可能机制。结果与对照组相比,apelin-13以剂量依赖的方式延长了实验动物的排珠时间(P<0.01),即抑制大鼠远端结肠的推进活动;N型胆碱能受体的阻断剂HEX能完全消除apelin-13对结肠推进的抑制作用;而M型胆碱能受体的阻断剂ATR以及肾上腺素受体阻断剂PHE和PRO都不能影响apelin-13在结肠推进上的作用。结论中枢apelin-13能剂量依赖的抑制大鼠远端结肠的推进,它的这种作用可能是通过N型胆碱能受体实现的。     

血管紧张素(1-7)的心血管效应

血管紧张素(1-7)是RAAS重要的生物活性物质之一,具有扩血管、抗增殖和抗凝血等效应,能拮抗血管紧张素Ⅱ等物质的生物活性。它可经血管紧张素Ⅰ、Ⅱ转化而来。血管紧张素转换酶2是Ang(1-7)的限速酶。Ang(1-7)主要通过其G-蛋白偶联受体Mas产生作用。     

肾血管性高血压大鼠脑室注射γ-氨基丁酸的心血管效应(英文)

GABA(100和200μg,icv)在肾血管性高血压大鼠(RVHR)产生较伪手术鼠更强的降压作用,尤术后4 wk,GABA降压增强的大部分可被预先icv卡托普利所取消,而ip卡托普利作用较弱,GABA icv还明显改善RVHR已下降的压力感受性反射敏感性,提示RVHR脑内GABA抑制功能不足;外源性GABA降压效应增强可能与其抑制脑内血管紧张素系统有关。     

卡维地洛对心肌梗死患者血清儿茶酚胺水平的影响

目的 探讨卡维地洛对心肌梗死后患者血儿茶酚胺水平的影响.方法 急性心肌梗死患者36例,随机分为实验组与对照组,实验组予卡维地洛治疗12个月,对照组则予以常规美托洛尔治疗12个月,比较两组血浆去甲肾上腺素和肾上腺素含量的变化并随访新的心脏事件发生情况.结果 在随访、监测12个月期间,实验组血浆去甲肾上腺素和肾上腺素浓度均明显低于对照组(P<0.05),实验组急性心力衰竭、再梗死、恶性心律失常及猝死的发生率亦显著低于对照组(P<0.05).结论 卡维地洛可使交感神经活性处于平稳状态,从而降低新的心脏事件发生率.     

血管紧张素-(1-7)对肾性高血压大鼠血压的影响

目的：探讨急性血管紧张素-（1-7）[Ang-（1-7）]对二肾一夹（2K1C）高血压大鼠血压的作用及其机制。方法：建立2K1C高血压大鼠模型后2周,经颈内静脉输注Ang-（1-7）,同时多导电生理仪记录有创颈动脉压演变。放免法测定血浆AngⅡ,酶法测定血清一氧化氮（NO）,酶免疫法测定血浆前列腺素E2（PGE2）、精氨酸加压素（AVP）,ELISA法测定血浆去甲肾上腺素（NE）。结果：Ang-（1-7）造成2K1C大鼠血压先升高,而后又降低到基础水平之下并维持该水平。与低血压状态相伴随,血清NO及血浆PGE2浓度升高（P〈0.01）,血浆NE及AVP浓度降低（P〈0.05）,血浆AngⅡ水平无明显变化。结论：在高肾素-血管紧张素系统活性状态下,Ang-（1-7）有降压作用,其降压机制与循环NO、PGE2浓度升高及AVP、NE水平降低有关。     

地尔硫唑对慢性充血性心力衰竭患者淋巴细胞膜β肾上腺素受体下调的影响(英文)

目的:研究钙拮抗剂地尔硫唑是否逆转慢性充德性心力衰竭(CHF)患者淋巴细胞膜β肾上腺素受体(β-AR)的下调.方法:同位素放射配基法测定地尔硫唑治疗前后CHF患者淋巴细胞β-AR密度,Fura 2-AM荧光指示法测定血小板胞内[Ca~(2 )]_i,放射免疫法测定血浆去甲肾上腺素(NE)浓度的变化.结果:CHF患者淋巴细胞β-AR密度低于对照组.血小板[Ca~(2 )]_i及血浆NE水平均高于对照组.地尔硫唑降低血小板[Ca~(2 )]_i,升高淋巴细胞β-AR密度.治疗前后血浆NE水平无显著变化.无论治疗前后,血小板[Ca~(2 )]_i与淋巴细胞β-AR密度均呈负相关.结论:地尔硫唑能够部分逆转心衰患者β-AR的下调,这种作用与血浆NE水平变化无关,而可能与降低细胞内[Ca~(2 )]_i有关.     

Central and peripheral sites for cardiovascular actions of dynorphin-(1-13) in rats

Dynorphin-(1-13) (i.v.) induced bradycardia and hypotension in artificially ventilated anaesthetized rats. These effects were prevented by MRZ 2266 BS. The bradycardia was inhibited by bilateral vagotomy whereas the fall in blood pressure was not sensitive to bilateral vagotomy and chlorpheniramine treatment. In pithed rats, dynorphin-(1-13) reduced heart rate. This bradycardia was prevented by MRZ 2266 BS but not by tertatolol and cimetidine. It is suggested that the dynorphin-(1-13)-induced effects result from the stimulation of central and cardiac kappa-opiate receptors.     

Enhanced antidepressant efficacy of sigma1 receptor agonists in rats after chronic intracerebroventricular infusion of beta-amyloid-(1-40) protein

Treatment of depressive symptoms in patients suffering from neurodegenerative disorders remains a challenging issue, since few available antidepressants present an adequate efficacy during pathological aging. Previous reports suggested that selective sigma(1) receptor agonists might constitute putative candidates. We here examined the pharmacological efficacy of igmesine and (+)-SKF-10,047 and the sigma(1) receptor-related neuroactive steroid dehydroepiandrosterone sulfate, in rats infused intracerebroventricularly during 14 days with the beta-amyloid-(1-40) protein and then submitted to the conditioned fear stress test. Igmesine and (+)-SKF-10,047 significantly reduced the stress-induced motor suppression at 30 and 6 mg/kg, respectively, in beta-amyloid-(40-1)-treated control rats. Active doses were decreased, to 10 and 3 mg/kg, respectively, in beta-amyloid-(1-40)-treated animals. The dehydroepiandrosterone sulfate effect was also facilitated, both in dose (10 vs. 30 mg/kg) and intensity, in beta-amyloid-(1-40)-treated rats. Neurosteroid levels were measured in several brain structures after beta-amyloid infusion, in basal and stress conditions. Progesterone levels, both under basal and stress-induced conditions, were decreased in the hippocampus and cortex of beta-amyloid-(1-40)-treated rats. The levels in pregnenolone, dehydroepiandrosterone and their sulfate esters appeared less affected by the beta-amyloid infusion. The sigma(1) receptor agonist efficacy is known to be inversely correlated to brain progesterone levels, synthesized mainly by neurons that are mainly affected by the beta-amyloid toxicity. The present study suggests that sigma(1) receptor agonists, due to their enhanced efficacy in a nontransgenic animal model, may alleviate Alzheimer's disease-associated depressive symptoms.     

Possible regulatory role of dynorphin-(1-13) on narcotic-induced changes in naloxone efficacy

Pretreatment of mice with a single injection of morphine, beta-endorphin, Leu-enkephalin, FK33824 or [D-Ala2-D-Leu5]enkephalin, for 3 h increased the ability of naloxone to antagonize the analgesic effects of morphine. However, dynorphin-(1-13) can only antagonize morphine, beta-endorphin or Leu-enkephalin induced increased naloxone efficacy but not FK33824 or [D-Ala2-D-Leu2]enkephalin. Dynorphin itself can also increase naloxone efficacy when treated alone. However, this effect can be prevented when animals are pretreated with dynorphin and naloxone together.     

apelin-13侧脑室注射对脂多糖诱导小鼠发热的缓解作用

目的探讨侧脑室注射apelin-13对小鼠体温的作用及对脂多糖诱导小鼠发热的解热作用。方法小鼠随机分为对照组,脂多糖50、150 ng组,apelin-13 3、10 nmol组,脂多糖150 ng+apelin-13 3 nmol组和脂多糖150 ng+apelin-13 10 nmol组。药物或生理盐水以10μL/min的恒定速度侧脑室注射,注射体积为4μL。给药后0.5、1.0、1.5、2.0、2.5、3.0、3.5、4.0 h分别监测记录各组小鼠的体温,计算各组小鼠在各时间点体温的变化。根据实验结果绘制温度变化曲线,并计算出曲线下面积(area under the curve,AUC)。结果与对照组比较,脂多糖150 ng组温度均显著升高(P0.05),引起发热效果明显,因此选择注射150 ng脂多糖作为模型组。侧脑室单独注射3、10 nmol apelin-13对小鼠温度变化没有明显影响。侧脑室注射3 nmol apelin-13在1.5 h降低150 ng脂多糖引起的发热(P0.05);而10 nmol apelin-13在1.5、2.0、3.0 h均降低150ng脂多糖引起的发热(P0.05)。与脂多糖150 ng组比较,脂多糖150 ng+apelin-13 10 nmol组体温AUC显著减少(P0.05);脂多糖150 ng+apelin-13 3 nmol组体温AUC虽然减少,但是并不具有显著性差异。结论中枢apelin-13对小鼠的体温没有影响,但侧脑室注射10 nmol apelin-13能够明显降低脂多糖引起的小鼠体温升高,具有缓解脂多糖诱导的小鼠发热作用。     

Acute subjective effects of dynorphin A(1-13) infusion in normal healthy subjects

Twelve healthy subjects with no history of substance abuse participated in a placebo-controlled single-blinded study of subjective response to acute i.v. administration of placebo and two doses of the natural shortened peptide sequence of the kappa-opioid agonist, dynorphin A(1-13) (low dose 120 micrograms/kg, high dose 500 micrograms/kg). Visual analog scales showed small but significant negative mood and positive drug effect 10 min post infusion in the high dose dynorphin compared to placebo infusion. The differences were no longer apparent at 30 min. These results show that dynorphin A(1-13), shown previously to have both neuroendocrine and modest analgesic effects, was well tolerated and produced modest transient subjective responses.     

Affinity profile at alpha(1)- and alpha(2)-adrenoceptor subtypes and in vitro cardiovascular actions of (+)-boldine

The present study examines the functional and binding affinities of the aporphine alkaloid, (+)-boldine, at different alpha(1)- and alpha(2)-adrenoceptor subtypes, namely, alpha(1A) (rat vas deferens and kidney) and its L-like state (rabbit spleen), alpha(1B) (guinea pig spleen, mouse spleen and rabbit aorta), alpha(1D) (rat aorta and pulmonary artery), at possible subtypes of prejunctional alpha(2)-adrenoceptors in rat and rabbit vas deferens and rat atrium, alpha(2D) in guinea pig ileum, cloned human alpha(1)-adrenoceptor subtypes A, B and D and alpha(2)-adrenoceptor subtypes A, B and C as well as rat alpha(2D)-adrenoceptors. Additionally, we investigated its Ca(2+) channel antagonism in vascular and cardiac preparations. (+)-Boldine had higher affinity at alpha(1)-adrenoceptor subtype A (pA(2)=7.46, pK(i)=7.21) compared with its L-like state (pA(2)=5.63) or subtype B (pA(2)=5.98- 6.12, pK(i)=5.79) and subtype D (pA(2)=6.18-6.37, pK(i)=6.09). Its affinities at alpha(2)-adrenoceptors in rat and rabbit vas deferens and rat atrium (pA(2)=6.02, 6.36, 6.06, respectively) were identical, but lower at guinea pig ileum alpha(2D)-adrenoceptors (pA(2)=4.38). (+)-Boldine displayed nearly undistinguishable affinity at cloned human alpha(2)-adrenoceptor subtypes A, B and C (pK(i)=6.26, 5.79 and 6.35, respectively), whereas its affinity at rat alpha(2D)-adrenoceptors was low (pK(i)=4.70). In perfused rat kidney, (+)-boldine inhibited K(+)-evoked vasoconstriction at doses 70-fold higher than diltiazem. In guinea pig Langendorff heart, (+)-boldine (10(-5) - 2 x 10(-4) M) was equieffective in increasing coronary flow and in depressing cardiac force, while lower concentrations already depressed heart rate. In papillary muscles from guinea pig, (+)-boldine (10(-6) - 10(-5) M) mainly prolonged the duration of action potential at levels >30% of repolarization. These data reveal that (+)-boldine, except for its moderate selectivity (15 to 25-fold) for alpha(1A)-adrenoceptors, does not discriminate between the alpha(1)-adrenoceptor subtypes B and D and alpha(2)-adrenoceptor subtypes A, B and C, at which the drug consistently displays micromolar affinity. In vascular and cardiac preparations, (+)-boldine, although being at least 50-fold weaker than diltiazem, shows Ca(2+) channel antagonistic properties but no specificity for coronary dilatation relative to cardiodepression.