延胡索乙素对大鼠垂体促肾上腺皮质激素(ACTH)分泌的刺激作用

鎮痛药嗎啡以及安定药氯丙嗪均有刺激垂体促腎上腺皮貭激素释放的作用.延胡索乙素具有类似嗎啡的鎮痛作用和类似氯丙嗪的安定作用,它是否也能引起垂体促腎上腺皮貭激素的释放是本文研究的問題. 实驗用体重80—150克的雄性大白鼠,以腎上腺維生素C含量的下降做为垂体促腎上腺皮貭激素释放的指标. 給大鼠皮下注射延胡索乙素50或70毫克/公斤(有效鎮痛和安定剂量)后,腎上腺維生素C含量明显下降,說明延胡索乙素有兴奋垂体腎上腺系統的作用。給去垂体大鼠注射延胡索乙素并不能引起腎上腺維生素C含量下降,說明延胡索乙素兴奋垂体-腎上腺系統的作用在于引起垂体促腎上腺皮貭激素的分泌,而不是直接兴奋腎上腺皮貭。給大鼠注射戊巴此妥鈉40毫克/公斤,或注射去氫皮貭醇(prednisolone)15毫克/公斤后,延胡索乙索引起垂体促腎上腺皮貭激素释放的作用消失,說明延胡索乙素这一作用的部位有可能是在下视丘.     

四种苯骈二氧六环化合物的腎上腺素能阻断作用

四种苯駢二氧六环化合物的結构式为: 小白鼠腹腔注射BD-3,933F,BD-1和BD-5的LD₅₀分別为0.1,0.20,0.26和0.22克/公斤,BD-3和933F組死亡多在1—3小时內,而BD-1和BD-5組死亡多在1—3天內。BD-5在小鼠能显著減低腎上腺素的毒性,而其他3药则不能。麻醉大白鼠和猫靜脉注射4药后均可引起降压,但4药间差异均不显著。BD-3,933F和BD-1使麻醉猫靜脉注射腎上腺素的升压引起反轉作用,而BD-5仅具抑制作用。对酪胺及去甲腎上腺素的升压,4药均可抑制。麻醉猫靜脉注射10毫克/公斤的933F有增血糖作用,BD-5注射20毫克/公斤才增高血糖。933F和BD-5对腎上腺素所引起的血糖及乳酸均无明显的抑制作用。因为BD-5同时阻断收縮和舒张血管的作用,但不引起腎上腺素的反轉作用,因此在治疗血管痙攣性疾患中可能比933F效果更好。     

正腎上腺素在内科治療休克之應用

正肾上腺素用于治疗休克,国外文献已有不少記载,但国内文献尚少記載。本文系我院用此药或并用他药治疗20例休克之初步总結。正腎上腺素之名称很多:有Norepinephrine, Nor-adrenaline, Arterenol, Levarterenol, Levophed, Merepinephrine等,一般常用名称为Npr-adrenaline。1904年Stolz氏及1905年Dakin氏首先综合合了消旋正腎上腺素(Racemic arterinol)。1910年Barger氏和Dale氏曾对正腎上腺素和腎上腺素之药理作用进行比較。正腎上腺素和腎上腺素在构造上极为相似(肾上腺素在氮上多一甲基),因此在药理作用上二者有相似之处。正腎上腺素对心脏血管系統方面的作     

狭叶萝芙木根生物碱的降压作用及机制

继中国蘿芙木之后,最近在云南又发現狹叶蘿芙木(Rauwolfia yunnanensis Tsiang var.angustifolia C.Y.Wu.)。其根生物碱对麻醉动物具降压作用,給犬靜脉注射1毫克/公斤后2小时內的降压面积为-32%,給猫靜脉注射3毫克/公斤的降压面积为-30%。同时測得中国蘿芙木根生物碱在犬的降压面积为-45%,猫为-29%。重复給药有快速耐受性。降压的同时呼吸呈兴奋,对心率影响不明显。降压作用与M-胆碱能反应系統、N-胆碱能反应系統以及內感受器都无关系?匝芤参拗苯幼饔?单側頸交感神經切除兔耳試驗发現,扩张血管的作用与交感神經有关。狹叶蘿芙木根生物碱可抑制腎上腺素或去甲腎上腺素的加压反应,也可抑制阻断頸总动脉血流和电刺激迷走神經或胫骨神經中枢端所致的加压反射。用脊猫試驗吋其降压作用大为減弱,但并不完全消除,降压面积仅为-14%。因此,其降压机制包括中枢和外周两方面,即对血管运动中枢的抑制作用和抗腎上腺素的作用。急性毒性試驗証明,狹叶蘿芙木根生物碱的毒性很小,小鼠口服2000毫克/公斤无死亡发生,动物呈現安靜状态。     

儿茶酚胺合成抑制剂

儿茶酚胺(catecholamine)在本文内专指在体内合成的带儿茶酚环的脂胺类,包括腎上腺素、去甲腎上腺素(NA)和儿茶酚乙胺(dopaminc,DA).腎上腺素是腎上腺髓貭的激素,而去甲腎上腺素是一种神經介貭,早所熟知.儿茶酚乙胺除作为前二者生物合成的前体外,本身可能和錐束外系的中枢功能有关。在高血压病的发病机制中,体内是否有儿茶     

腎素、血管紧張素与醛固酮

腎素、血管紧张素与醛固酮之間的关系是近年来引人注意的問題。目前一般认为腎脏在調节腎上腺分泌醛固酮的机制上起着重要的作用。在一定条件下腎脏可以分泌一种醛固酮刺激素(Aldosterone stimulating hormone)。此激素可能就是腎素或許是相近的物质。因此构成了腎—腎上腺之間的調节系統。国外已对此问題做了許多研究工作,本文仅綜述所閱文献作一簡要介紹。     

二仙合剂的降压及其药理研究

二仙合剂可治疗妇女高血压,在腎型高血压狗也有降压效果。本文用5种高血压大白鼠(神經型、腎型、腎上腺燙伤型、睾丸切除型及卵巢切除型)来比較降压作用,并观察性周期、前庭时值及某些加压物质的升压反应。每天灌胃二仙合剂10克/公斤,共2周,神經型、腎型及睾丸切除型的降压面积%分别为-9,-11及-15%,与同型对照組比較,降压“显著”,腎上腺燙伤型及卵巢切除型的降压“不显著”。每天灌服二仙合剂10克/公斤,共7周,对未成熟大白鼠生长及性腺发育无影响。对神經型、腎型及腎上腺燙伤型雌鼠的性周期紊乱亦无糾正作用。二仙合剂能延长腎型高血压鼠的前庭时值,但在其他型则变化不显著。无明显对抗去甲腎上腺素及垂体后叶素的加压反应的作用。     

急性腎小管坏死(三)

处理: 一、早期防治: (一) 去除病因: 1.糾正水、电解质平衡及抗休克治疗:应尽早恢复体液的丟失,并应尽可能按照所丢失的体液性质予以糾正。至于在休克期应用去甲腎上腺素的問題近年来的研究証明,似对腎脏有不利影响,Chung氏对休克期应用大量去甲腎上腺素治疗,但終于死亡的患者作了病理检查,均呈腎小管广泛性坏死。Langston氏等的研究証明,去甲腎上腺素在小剂量0.00006毫克/公     

药理学及毒物学

Ⅶ-42 关于对抗氯駢嗪的降低血压和抗腎上腺素的作用 1958,45,[5],65 本文作者研究了去甲腎上腺素,麦撒同,苯丙胺,印防己毒素,山梗菜硷,茶硷,腦垂体后叶素,麻黄硷,去氧麻黄硷,五甲烯四氮唑,可拉明,士的宁,咖啡因,β-tetra-hydronaphtylamine,10-allyl-phenothiazine,10-anyl-2-chlorphenothiazine,pyrogenal十七个药的对抗氯駢嗪的降低血压和抗腎上腺素作用。     

儿茶酚胺与心脏的关系

去甲腎上腺素(NA)、腎上腺素(A)等对心脏的药理作用数十年前已被发現,此后又发现在許多动物心肌本身即含有儿茶酚胺(CA)类物貭。更由于近年来NA及A等微量測定方法的发展,解决了心肌中CA含量的問題。同时又有CA释放药、CA释放阻断药、交感胺代謝酶的抑制药及NA的前体等药的发現,以及带有神經离体标本的运用等,均为此創造条件,更促进CA与心脏关系的研究,进一步闡明心肌中含有的CA在药理、生理及病理方面的意义。本文仅就心肌CA以下的几个方面,复习文献,加以綜述。     

The vascular changes after ephedrine tachyphylaxis.

The changes elicited after ephedrine tachyphylaxis in the dog femoral and rabbit aortic strips isolated from the untreated and ephedrine pre-treated animals have been studied. In untreated strips, ephedrine exhibited dose-dependent contractions which were blocked by phenoxybenzamine. These contractile responses to ephedrine were reduced after pre-treatment with ephedrine in vivo. In rabbit aortic strips previously contracted with noradrenaline or KCL, ephedrine induced dose-dependent relaxations at high concentrations, which were not affected by propranolol. These relaxation responses were likewise diminished after ephedrine. Dose-related contractile responses to noradrenaline were potentiated at low concentrations and depressed at high concentrations after ephedrine whereas those to adrenaline were inhibited over the entire agonist range. Responses to KCL were not affected. These reductions in the responses to noradrenaline and adrenaline after treatment with ephedrine in vivo were inhibited by icreased calcium2+ concentration. From the results, it can be presumed that the observed changes in vascular responsiveness may be partially involved in the development of ephedrine tachyphylaxis.     

心房肽Ⅲ对人体血管作用的差异性

采用离体人脐动脉,人胃网膜右动脉,家兔及大白鼠胸主动脉肌条,观察APⅢ和NP的作用。APⅢ75nmol/l对由NA3μmol/l,5-HT1μmol/l,HT10μmol/l,PE 1μmol/l收缩的家兔及大白鼠胸主动脉肌条具有明显松弛作用,对由上述药物及KCl 80mmol/l,PGF_(2α)10μmol/l所收缩的人脐动脉及人胃网膜右动脉并无松弛作用。NP 1μmol/l对由NA3μmol/l,5-HT 1μmol/l,HT 10μmol/l等所收缩的两种人血管都有明显松弛作用,并能降低血管基本张力。结果提示:APⅢ对家兔及大白鼠的胸主动脉有松弛作用,但对人脐动脉及人胃网膜右动脉无松弛作用,表明APⅢ对血管的作用可能具有动物种属或血管种类差异性,NP则有较普遍的血管松弛作用。     

Action of dexamphetamine on 5-hydroxytryptamine receptors

Dexamphetamine contracted isolated preparations of rat stomach, dog retractor penis, rabbit aorta, rabbit uterus and all sections of guinea-pig ileum. Adrenaline inhibited rat stomach and all but the terminal 10 cm of guinea-pig ileum, but contracted dog retractor penis, rabbit aorta, rabbit uterus and the terminal portion of the guinea-pig ileum. 5-Hydroxytryptamine contracted all five preparations. Responses to dexamphetamine and 5-hydroxytryptamine were not blocked in preparations protected by a high concentration of either drug during exposure to phenoxybenzamine in a dose which usually caused block. Responses to dexamphetamine and 5-hydroxytryptamine were blocked in preparations protected by adrenaline. Responses to dexamphetamine in dog retractor penis, rabbit aorta and rabbit uterus were not reduced in preparations from animals treated with reserpine or after cocaine, indicating that the contraction is not mediated by released noradrenaline. It is concluded that dexamphetamine acts directly on 5-hydroxytryptamine receptors in these smooth muscles and therefore cannot be regarded as a true sympathomimetic amine.     

An action of 5-hydroxytryptamine on adrenaline receptors

Contractions of isolated strips of cat spleen due to 5-hydroxytryptamine, adrenaline, histamine and acetylcholine were antagonized by phenoxybenzamine. Responses to both 5-hydroxytryptamine and adrenaline were not blocked in strips which were protected by a high concentration of either 5-hydroxytryptamine or adrenaline throughout exposure to phenoxybenzamine. The contraction due to a large dose of 5-hydroxytryptamine lasted less than 1 hr even when the drug was still present. Strips thus desensitized to 5-hydroxytryptamine responded normally to acetylcholine and histamine but did not respond to adrenaline. The actions of 5-hydroxytryptamine and adrenaline were blocked by 2-bromolysergic acid diethylamide or by dihydroergotamine. These results indicated that 5-hydroxytryptamine and adrenaline act on the same receptors. Cocaine potentiated the action of adrenaline but inhibited the action of 5-hydroxytryptamine. The sensitivity to 5-hydroxytryptamine of spleen strips from cats treated 24 hr earlier with reserpine was only one-fiftieth of that of normal strips. Cocaine potentiated the action of 5-hydroxytryptamine on strips from reserpine-treated cats. A high concentration of 5-hydroxytryptamine in spleen strips from reserpine-treated cats and in cocaine-treated strips prevented phenoxybenzamine from blocking the actions of adrenaline. The effects of tyramine on spleen strips almost exactly paralleled the effects of 5-hydroxytryptamine. Strips showing tachyphylaxis to tyramine did not respond to 5-hydroxytryptamine. It is concluded that 5-hydroxytryptamine has a dual action, viz., a major action due to release of stored noradrenaline and a minor direct action of adrenaline receptors.     

α-adrenoceptors in human peripheral lung

In this study, strips of human peripheral lung tissue were used to investigate the presence of a population of α-adrenoceptors. Lung strips contracted in response to stimulation with noradrenaline, adrenaline, methoxamine and phenylephrine. In the presence of propranolol, responses to noradrenaline were antagonized by phentolamine and a pA₂ of 7.29 was obtained. It is concluded that human peripheral lung tissue contains a pharmacologically distinct population of α-adrenergic receptors.     

Adrenoceptive receptors in the duodenum,aorta and atria of the rabbit

pA₁₀ values for the α-receptor blocking drug phentolamine against adrenaline, noradrenaline and phenylephrine were determined in rabbit aorta and duodenum, and for the β-receptor blocking drug propranolol, against adrenaline, noradrenaline and isoprenaline in rabbit atria and duodenum. The values for phentolamine against different amines were found to be similar, varying by less than half a log unit, between or within the tissues, as were the values for propranolol. These data provide quantitative evidence that α-receptors in the aorta and duodenum are similar, as are the β-receptors in the atria and duodenum, even though both types of receptor serve divergent functions in different tissues.     

脑内注射拟交感胺的鎭痛作用比较

In mice, the analgesic ED₅₀ of intracerebral injection of adrenaline, noradrenaline, ephedrine, amphetamine, and tyramine was 0.84, 1.2, 18.2, 4.8, and 31.5μg respectively as determined by the method of i.p. tartar emetic induced writhing. It indicates that the analgesic activity of sympathomimetic amines requires certain structural specificity. Employing the method of radiant heat focusing on the rabbit nose, only a part of the animals with intraventricular injection of 0.5 mg of noradrenaline showed an analgesic action of very short duration. Since the analgesic effect of intraventricular noradrenaline is so weak, the present results support the view that morphine analgesia is not an indirect action via central noradrenaline liberation.     

Rabbit aorta: electrical properties and agonist-induced depolarization

The resting membrane potential of the smooth muscle cells of strips of rabbit aorta varied between -50 to -60 mV. No spontaneous spike discharges were observed. The membrane of the myocytes showed a marked outward rectifying property. The rabbit aorta had cable properties with a space constant (lambda) of 1.54 +/- 0.04 mm. Parallel with a progressive mechanical tension development, noradrenaline and the alpha 1-agonist methoxamine depolarized the membrane in a concentration-dependent manner up to -40 mV. Stimulation of aortic alpha 1-adrenoceptors by noradrenaline reduced the steepness of the current-voltage relationship and diminished the space constant from 1.54 to 0.8 mm, indicating a decrease in membrane resistance. No action potentials were evoked by noradrenaline. The alpha 2-agonist, B-HT 920, produced only a slight contraction and virtually no change in membrane potential. As compared to noradrenaline or methoxamine, angiotensin II was a partial agonist to induce contraction, with an intrinsic activity of 0.6-0.7. The octapeptide depolarized the membrane of the myocytes in a concentration-dependent manner and to a maximal extent similar to that observed for alpha 1-adrenoceptor stimulation. No action potentials appeared with angiotensin II. In contrast to earlier reports, depolarization did occur in the rabbit aorta in response to noradrenaline. The demonstration of depolarization raises the possibility that contraction of this blood vessel occurs through electromechanical and not or not solely through pharmacomechanical coupling when receptors for two important endogenous vasoconstrictors, noradrenaline and angiotensin II, are stimulated.     

BETA-ADRENORECEPTORS OF THE CAT NICTITATING MEMBRANE

• 1 The relaxant effects of isoprenaline, salbutamol, adrenaline and noradrenaline on the partially contracted isolated nictitating membrane of the cat were determined in the absence and the presence of α-adrenoreceptor blockade.
• 2 It was possible to demonstrate significant relaxant effects of isoprenaline and salbutamol in the absence as well as in the presence of α-adrenoreceptor blockade. However, the relaxant effects of adrenaline and noradrenaline could not be demonstrated in the absence of α-adrenoreceptor blockade.
• 3 Molar concentrations (EC₃₀) of isoprenaline, salbutamol and adrenaline causing 30% relaxation of the tone did not significantly differ from each other; EC₃₀ of each of these agents was significantly less than that of noradrenaline.
• 4 β₁-Adrenoreceptor antagonist metoprolol was less potent than β₂-antagonist H 35/25 in antagonizing the effect of salbutamol; metoprolol was more potent than H 35/25 in antagonizing noradrenaline. Both these agents were effective antagonists of isoprenaline; however, metoprolol and H 35/25 in combination produced greater antagonism of isoprenaline than did each antagonist separately.
• 5 It is concluded that the cat nictitating membrane possesses both β₁- and β₂-adrenoreceptors which are responsible for the relaxant effects of sympathomimetic agents. A study of these receptors is, however, complicated by concomitant stimulation of α-adrenoreceptors.

     

The inhibitory action of two thrombin inhibitors (TI-189 and TI-233) on the contractile responses to 5-hydroxytryptamine and prostaglandin endoperoxide analogue (U-44069) in isolated vascular strips.

1. Two arginine derivatives that were developed as thrombin inhibitors (TI-189 and TI-233) selectively inhibited the 5-hydroxytryptamine (5-HT)-induced contraction of rabbit aortic strips in a competitive manner. The PA2 values of TI-189 and TI-233 were 5.24 +/- 0.21 and 6.23 +/- 0.32 respectively. 2. Even at 10(-4) M they had no inhibitory effect on the contractile response to noradrenaline (NA), histamine, prostaglandin E2 (PGE2), PGF2 alpha, arachidonic acid or potassium in rabbit aortic strips. 3. In dog basilar and coronary arterial strips and also in rat fundus, both agents inhibited the 5-HT response in a non-competitive manner. 4. At 10(-5) M, TI-233 but not TI-189 antagonized effects of NA and KCl in the dog basilar and coronary arteries. 5. These arginine derivatives decreased the contractile responses induced by a prostaglandin endoperoxide analogue (U-44069) in rabbit aorta and in dog basilar and coronary arteries but there was no evidence for competitive antagonism. 6. These results indicate that the arginine derivatives are competitive antagonists selective for 5-HT receptors in rabbit aorta.