碘化二甲基木防己碱对清醒及急性肾型高血压大鼠的降压作用

前文报道,iv碘化二甲基木防己碱(DTI)对麻醉狗、猫、兔及大鼠均有降压作用,其降压作用可能与阻断交感神经节的作用有关。本文研究了DTI长期po对清醒和麻醉大鼠的降压作用及iv对急性肾型高血压大鼠血压的影响。     

小唐松草碱的降压作用

小唐松草碱(ocoteine)1～10 mg/kg iv对麻醉、清醒的正常血压大鼠和肾性高血压大鼠均有迅速而持久的降压作用,脑室内注射给药也有明显的降压作用。切断双侧迷走神经合用阿托品,及用苯海拉明不影响 ocoteine的降压作用。在毁脊髓大鼠,ocoteinc 1～3mg/kg使甲氧明的量效曲线平行右移,而不影响B-HT920的量效曲线。结果提示ocoteine选择性阻断血管性平滑肌突触后α_1受体,并可能具有中枢性降压作用;其降压作用不是通过迷走神经或释放组胺。     

苦马豆总黄酮甙的降压作用及其机理

麻醉动物、清醒动物以及自发性高血压大鼠,iv苦马豆总黄酮甙后,均有显著的降压作用,起效快,持续时间短。降压机理与交感神经节阻断作用和直接扩张血管作用有关。血流动力学实验表明,苦马豆总黄酮甙对心肌收缩力和心率均无明显影响。由于外周扩血管作用而使总外周阻力明显降低。     

中枢与外周α-肾上腺素能受体激动效应不一致性的原理分析

对戊巴比妥钠麻醉家兔,静脉注射α-肾上腺素能受体拮抗剂育亨宾(Yohimbine)或γ-氨基丁酸(GABA)受体拮抗剂苦味毒(picrotoxin)均可明显对抗侧脑室注射氯压定(clonidine)的降血压作用。但是育亨宾不能阻断侧脑室注射GABA的中枢降压作用,而苦味毒则能完全阻断其降压效应。 家兔经GABA合成抑制剂氨基脲(Semicarbazide)静脉注射予处理后,动物于给药后3～4小时出现强烈惊厥,说明脑内GABA已降低到一定水平。此时用局部麻醉剂及肌松剂处理,在人工呼吸情况下,氯压定静脉注射的降压作用比不给氨基脲予处理的对照组动物显著减弱。 以上结果启示,中枢肾上腺素能受体激动而产生的降压作用有可能是通过GABA能抑制性神经元而实现。     

槐胺碱的心血管作用

槐胺碱(Sa)对麻醉猫、兔和大鼠均有明显的降压作用,降压机理与交感神经节阻断作用和直接扩张外周血管有关。离体心脏实验表明,Sa有负性频率,增加冠脉流量和一定的正性肌力作用。Sa能推迟乌头碱诱发的大鼠心律失常发生时间,缩短心律失常的持续时间,并能降低氯仿诱发的小鼠室颤发生率。其对实验性血栓形成和ADP诱导的血小板聚集作用无影响。     

栀子的药理作用

梔子煎剂和醇提取物对麻醉或不麻醉动物(猫、兔、大白鼠),不论口服或腹腔注射,均有持久性降压作用。静脉注射迅速降压而维持时短。梔子的降压作用与肾上腺素及胆碱生化反应系统,神经节阻断,组织胺的释放均无关系。静脉注射普鲁卡因对梔子的降压作用无影响,但切断迷走神经后,则作用减弱或消除。注射阿托品亦可取消其降压作用,其作用部位似在延脑副交感中枢,梔子醇提取液对家兔及大白鼠离体肠管平滑肌,低浓度(2.5×10~(-4))兴奋,高浓度(2×10~(-2))则抑制,小白鼠急性腹腔注射,LD_(50)为27.45克/公斤。     

青藤碱的药理作用Ⅳ.青藤碱降压机制的研究

给麻醉狗、大白鼠和兔静脉注射青藤碱盐酸盐后,皆可产生肯定的降压作用.(?)只狗注射青藤碱(1毫克/公斤)后,平均降压面积为-40±3%.应用同量的药物反复注射三种动物都能出现快速耐受现象;以狗最为明显.在位狗心实验中发现青藤碱在降压同时并不抑制心脏,抗组织胺药不能影响其降压效果,对于M-胆碱反应系统并无影响.本药具抗肾上腺素作用和神经节阻断作用,且能抑制多种中枢性加压反射,故其降压机制可能系抗肾上腺素、阻断神经节和中枢作用的结果.     

中枢与外周α-肾上腺素能受体激动效应不一致性的原理分析

对戊巴比妥钠麻醉家兔,静脉注射α-肾上腺素能受体拮抗剂育亨宾(Yohimbine)或γ-氨基丁酸(GABA)受体拮抗剂苦味毒(picrotoxin)均可明显对抗侧脑室注射氯压定(clonidine)的降血压作用。但是育亨宾不能阻断侧脑室注射GABA的中枢降压作用,而苦味毒则能完全阻断其降压效应。家兔经GABA合成抑制剂氨基脲(Semicarbazide)静脉注射予处理后,动物于给药后3～4小时出现强烈惊厥,说明脑内GABA已降低到一定水平。此时用局部麻醉剂及肌松剂处理,在人工呼吸情况下,氯压定静脉注射的降压作用比不给氨基脲予处理的对照组动物显著减弱。以上结果启示,中枢肾上腺素能受体激动而产生的降压作用有可能是通过GABA能抑制性神经元而实现。     

栀子的药理作用

梔子煎剂和醇提取物对麻醉或不麻醉动物(猫、兔、大白鼠),不论口服或腹腔注射,均有持久性降压作用。静脉注射迅速降压而维持时短。梔子的降压作用与肾上腺素及胆碱生化反应系统,神经节阻断,组织胺的释放均无关系。静脉注射普鲁卡因对梔子的降压作用无影响,但切断迷走神经后,则作用减弱或消除。注射阿托品亦可取消其降压作用,其作用部位似在延脑副交感中枢,梔子醇提取液对家兔及大白鼠离体肠管平滑肌,低浓度(2.5×10^-4)兴奋,高浓度(2×10^-2)则抑制,小白鼠急性腹腔注射,LD₅₀为27.45克/公斤。     

软珊瑚二萜葡糖苷的降压作用研究

静脉注射软珊瑚二萜葡糖苷(soft coral diterpene glucostde，SCDG)，能明显降低麻醉大鼠颈动脉压．量效关系明显，未见快速耐受现象；侧脑室给药．未见有降压效应；SCDG对肾上腺素的升压有增强效应；SCDG拮抗烟碱的升压作用；六甲双铵降压后SCDG不再降压。提示SCDG的降压机制可能和神经节阻断有关，而和中枢．外周M受体、a受体无关。     

碘化二甲基木防己碱对清醒及急性肾型高血压大鼠的降压作用

In acute renal hypertensive rats, the blood pressure could be reduced from 148.8±7.9 mmHg to 123.6±9.3 mmHg by intravenous injection of dimethyl trilobine iodide (DTI) at the dosage of 0.5 mg/kg. The hypotensive effect persisted more than 40 minutes.DTI also lowered the blood pressure of unanesthetized rats by feeding 3～10 mg/kg daily for 28 days, but it did not affect the SGPT of rats.     

Hypotensive and Vasorelaxing Activities of a Lectin from the Edible Mushroom Tricholoma mongolicum

Abstract: A lectin, which exerted a hypotensive action in rats after intravenous injection via the jugular vein, was isolated from the mycelia of the edible mushroom Tricholoma mongolicum. The lectin possessed a molecular weight of 37 K and its hypotensive activity was dose-dependent. Administration of the lectin at a dose of 10 mg/kg body weight caused a mean arterial blood pressure reduction of 95.3±7.4 mmHg. The lectin's hypotensive action was not mediated via autonomic ganglion transmission, α-adrenoceptors, β-adrenoceptors, cholinergic receptors, histaminergic receptors, nor the renin-angiotensin system, but it was probably mediated through vasorelaxation via adenosine A2 receptors and/or nitric oxide production.     

Chronic hypotensive effects of losartan are not dependent on the actions of angiotensin II at AT 2 receptors.

We have previously demonstrated the chronic hypotensive effects of the AT1 antagonist, losartan, in normotensive, salt-replete rats. One explanation for this response is a reduction in vascular resistance due to blockade of AT1 receptors. Another explanation is that increases in angiotensin II levels during losartan administration can bind to AT2 receptors. Studies suggest that binding of angiotensin II at AT2 receptors lowers arterial pressure by vasodilation. We hypothesized that the chronic effects of losartan are mediated by activation of angiotensin II effects at AT2 receptors. We tested this hypothesis by infusing the AT2 receptor antagonist, PD123319 (74 mg/kg/day), in conjunction with losartan (10 mg/kg/day) for 10 days in rats and compared the hypotensive response in rats treated with losartan alone. After 6 days of treatment, arterial pressure decreased similarly in losartan (-21 +/- 2 mm Hg) and losartan+PD123319 (-23 +/- 2 mm Hg) treated rats. However, by day 10 of the infusion, arterial pressure had decreased to a greater extent (p < 0.05) in rats treated with losartan and PD123319 (-31 +/- 2 mm Hg) compared with rats treated with losartan alone (-22 +/- 2 mm Hg). We conclude that the hypotensive effects of losartan are not dependent on the actions of angiotensin II at AT 2 receptors in normotensive, salt-replete rats.     

Age-related hypotensive effect of atropine in unanesthetized spontaneously hypertensive rats

Intravenous injection of atropine (0.5–20 mg/kg) produced a dose- and age-dependent decrease in the mean arterial pressure (MAP) of conscious spontaneously hypertensive (SH) rats 11–20 weeks of age. No effect on blood pressure occurred in age-matched Wistar-Kyoto (WKY) controls; however, heart rate was increased in both groups. In contrast to atropine, the same doses of methylatropine increased MAP and heart rate in both SH and WKY rats. Methylatropine also failed to modify the hypotensive effect of atropine in SH rats. The difference between the effects on blood pressure of atropine and methylatropine in SH rats was not seen when the animals were anesthetized with pentobarbital. In this case both agents reduced MAP. Intracerebroventricular (i.c.v.) injection of atropine in doses up to 200 μg in SH rats failed to modify MAP and was without effect on the hypotensive response to intravenous injection of atropine. Likewise, i.c.v. injection of hemicholinium-3 (which reduced MAP in SH rats) failed to modify the hypotensive effect of atropine. However, intravenous injection of atropine (10 mg/kg) prevented the hypotensive effect of hemicholinium-3. Theser results are discussed in terms of central and peripheral muscarinic mechanisms.     

Opiate antagonists reverse the centrally mediated antihypertensive action of propranolol in spontaneously hypertensive rats

In anesthetized spontaneously hypertensive rats naltrexone, 2 mg/kg i.p., inhibited the hypotension and bradycardia caused by intracisternal injection of (±)-propranolol. Naltrexone and naloxone also reversed the antihypertensive effect of chronic oral treatment with propranolol (60 mg/kg per day from age 4–14 weeks) in unanesthetized spontaneously hypertensive rats, whereas in untreated littermates the opiate antagonists had insignificant effects on blood pressure and heart rate.     

甲基莲心碱对正常及高血压大鼠血流动力学的影响

iv甲基莲心碱(Nef)6 mg/kg于正常血压、肾性高血压、DOCA盐型高血压大鼠,在血压下降的同时,伴有LVSP,±(dp/dt)max,(dp/dt)P~(-1)的降低,正常血压及肾性高血压大鼠LVSP~-(dp/dt)P~(-1)环缩小,其斜率变小,心率短时变慢,LVEDP变化不明显。iv Nef 2 mg/kg于Wistar高血压大鼠时,仅明显降低血压,而对其它血流动力学指标无明显影响,Nef降低舒张压的作用大于降低收缩压。猫后肢灌流实验证明Nef有明显降低血管阻力的作用。结果表明Nef的降压作用可能由于扩张外周血管所致。     

间硝苯啶、硝苯啶与尼群的平对动物降压作用的比较性研究

在清醒正常血压大鼠、免以及肾型高血压大鼠,比较了m-nif、nif及nitr的降压强度,和降压的时间动态过程,三药的降压作用与对照组及自身前后对比,统计学上均非常显著。m-nif与nitr降压持续时间较nif长。从清醒正常血压大鼠降压的量效关系比较,m-nif、nif和nitr的ED₅₀)分别为33.7±3.4,45.6±3.6和51.2±4.1 mg/kg(即90±9,132±10,142±11μmol/kg)。按克分子量计算对比m-nif的降压强度最大,nitr最弱。但三药对正常血压及肾型高血压动物的降压作用,按组间对比,无统计学差异。     

臭梧桐的药理研究 Ⅰ.臭梧桐热浸剂及提出物的毒性和降血压作用

1.本文就臭梧桐的一般性质作了实验性研究,结果证明其降血压成分易溶于水,难溶或不溶于乙醚、乙醇和氯仿,对热稳定,在碱性溶液中可被氯化钙沉淀出来。臭梧桐降血压效果可因产地而不同。开花前的和新鲜的臭梧桐降血压作用分别较开花后的和经长时间保存的要强。2.臭梧桐毒性甚小,其热浸剂和提出物给小鼠静脉注射时半数致死量分别为19.4克/公斤和0.98±0.075克/公斤。给大鼠每天用热浸剂(0.25—2.5克/公斤)灌胃经60天,除少数动物出现安静、轻度收缩压下降和大便变稀外,未发现其他毒性反应。3.臭梧桐提出物(50—100毫克/公斤)和热浸剂(150毫克/公斤)给麻醉大鼠和狗静脉注射时,可引起两度血压下降,但肌肉注射或经口给药,仅引起第二度降血压作用,其作用可维持2—3小时。静脉注射煎剂(麻醉大鼠和狗实验)仅出现第一度降血压作用,经口给药时无效。乙醚、乙醇和氯仿的浸出液不论静脉注射或经口给药,均不引起麻醉动物的血压下降。给肾型高血压大鼠每天经口投予臭梧桐热浸剂(0.5—5克/公斤)和提出物(50毫克/公斤)时,给药的第3—10天卽口出现血压下降,在给药的第二周和停药后的第一周,血压下降最明显,最大降血压作用可达原值的57.4%。多数高血压大鼠的血压在停药后的第二周恢复,少数在停药的2—4天或4周后恢复。     

Inhibition of sympathetic nerve activity by acute administration of the tricyclic antidepressant desipramine.

In rats anesthetized with pentobarbital/chloral hydrate, the i.v. injection of desipramine (0.3 mg/kg) caused a rapid fall in mean arterial blood pressure accompanied by a reduction in efferent renal nerve integrated activity. A similar reduction in electrical activity was seen in the preganglionic splanchnic nerve. Pretreatment of the rats with yohimbine (0.3 mg/kg) increased renal nerve activity by 20%, and the decrease in blood pressure and renal nerve activity elicited by a subsequent dose of desipramine was blocked. I.v. injection of prazosin (0.05 mg/kg) caused a reduction in systemic blood pressure. The hypotensive effect of a subsequent dose of desipramine was largely blocked, whereas the fall in renal nerve activity was attenuated, but still present. The data are consistent with an action of desipramine to reduce central sympathetic tone by increasing the release of endogenous noradrenaline which acts on alpha 2-adrenoceptors at CNS sites controlling sympathetic activity. An additional involvement of central alpha 1-adrenoceptors cannot be ruled out.     

Elevation in arterial blood pressure following the development of tachyphylaxis to peroxynitrite

The systemic administration of peroxynitrite produces transient reductions in mean arterial pressure and vascular resistances in anesthetized rats. The repeated administration of peroxynitrite results in tachyphylaxis. We now report that anesthetized rats (n = 8) treated with peroxynitrite (10 injections of 10 μmol/kg i.v.) subsequently develop increases in mean arterial pressure (20 ± 4%) and hindquarter (153 ± 28%), renal (93 ± 21%), and mesenteric (133 ± 25%) vascular resistances. These findings suggest that the in vivo production of peroxynitrite may contribute to the pathogenesis of hypertension.