紫菜降血压肽大鼠体内降压效果研究

目的观察紫菜降血压肽对高血压大鼠(SHR)和京都Wistar大鼠(WKY)的降压效果,并与降压药物卡托普利的作用效果比较。方法分别以500、1 000和1 500 mg.kg-1剂量的紫菜降血压肽一次性给药后,每隔2 h测量大鼠收缩压(SBP),连续测量8 h;长期实验持续4 w,每天1 500 mg.kg-1灌胃一次,每隔1周测量一次SBP、心率及体重。结果 SHR给予紫菜降血压肽后,血压均显著下降;而正常血压大鼠WKY服用紫菜降血压肽后血压没有显著变化,服用卡托普利血压仍保持显著下降的趋势。结论紫菜降血压肽对SHR具有显著的降压效果,长期服用可稳定血压,对正常血压大鼠无明显影响;卡托普利对SHR的降压效果虽高于紫菜降血压肽,但会导致正常大鼠血压过低。     

几种甾体避孕药对肾型及去氧皮质酮型高血压大鼠血压的影响

避孕甾体激素甲孕酮、甲地孕酮、氯地孕酮及炔诺酮在约相当于临床400～800倍剂量(按体重计)皮下注射,或加有和临床用避孕药相应比例的炔雌醇口服,对肾型高血压大鼠均有轻缓的降压作用。其中以甲地孕酮和氯地孕酮显著。但降压程度最多也不过为原血压的15%左右。降压的进展缓慢,停药后血压多能逐渐恢复。以相同剂量的甲地孕酮和炔诺酮给DOCA型高血压大鼠皮下注射,也得到同样结果。以上述实验中作用最强的甲地孕酮,按临床50倍剂量,给予肾型高血压或正常大鼠口服,虽连续服药21天,对血压均无任何影响。     

复方降压灵搽剂降血压作用的实验研究

目的 研究复方降压灵搽剂的降血压作用.方法 选用自发性高血压大鼠及药物性急性高血压犬,用HX-Ⅱ型小动物血压测量器,测压导管、流量记录仪、多导生理记录仪、测量记录复方降压灵搽剂对高血压模型大鼠及家犬血压、心率、外周阻力、心输出量、左心室内压、左心室作功指数等心脏血流动学的影响.结果 复方降压灵搽剂能降低自发性高血压大鼠、药物性急性高血压家犬的血压,(P＜0.05～0.01);降低药物性急性高血压犬的左心室内压、外周血管总阻力、心输出量、左心室作功指数,(P＜0.05～0.01).结论 复方降压灵搽剂有一定的降血压作用.     

厄贝沙坦氢溴酸盐的毒理学和药效学研究

目的比较厄贝沙坦氢溴酸盐与厄贝沙坦的毒性和药效。方法采用无创血压测量比较了厄贝沙坦氢溴酸盐、厄贝沙坦对自发性高血压大鼠血压的影响。分别ip、ig给药,观察两种药物的半数致死量(LD50),对心率、呼吸以及动物自主活动的影响。结果自发性高血压大鼠的血压明显高于非自发性高血压大鼠,给予厄贝沙坦氢溴酸盐、厄贝沙坦后血压均降至正常水平,且两种药物的降压作用差异无显著性,但厄贝沙坦氢溴酸盐的药效持续时间更长。厄贝沙坦氢溴酸盐、厄贝沙坦对动物的呼吸、心率以及自主活动的影响无差异,但厄贝沙坦氢溴酸盐的LD50明显高于厄贝沙坦。结论厄贝沙坦氢溴酸盐具有和厄贝沙坦相同的降压作用,但是作用时间更长,安全性更高。     

依那普利对实验性高血压的降压作用

用高血压实验模型研究了依那普利(1)的抗高血压作用。口服1或3 mg/kg 对二肾型高血压大鼠具降压作用;但一肾型高血压大鼠降压则需较高剂量。1对自发性高血压大鼠能显著降低血压。兔静注10.3mg/kg,100 min内血管紧张素Ⅰ的升压作用可被抑制。     

乌菊降压丸药效学实验

目的 :对乌菊降压丸的药理作用进行实验研究。方法 :以正常血压大鼠和自发性高血压大鼠 (SHR )的血压和心率为动物模型 ,观察乌菊降压丸的药效作用。空白对照组给予相应量的0 5 %羧甲基纤维素钠 ;阳性对照组给予牛黄降压丸2g/kg;实验组给予乌菊降压丸 ,高、中、低剂量分别为1 2、0 6、0 2g/kg。灌胃给药 ,qd ,连续15d。分别观察并记录给药后10、20、30、45、60、90、120、240min时的血压和心率变化。结果 :乌菊降压丸高、中剂量对SHR分别在20、30min起效 ,血压开始下降 ,心率开始减慢 ,分别维持3h和1h ,4h和2h恢复原来水平。结论 :乌菊降压丸对正常血压大鼠的血压和心率无明显影响 (P>0 05) ,但有一定降低趋势 ;对SHR连续给药15d后具有明显降压作用和减慢心率的作用 (P<0 05) ;高剂量组有较好的降压效果     

养血清脑颗粒对收缩压影响的实验研究

目的研究养血清脑颗粒(降血压药)对自发性高血压大鼠(SHR)的降压作用。方法用SHR模型和大鼠尾动脉脉搏测压法,观察养血清脑颗粒(31.5,15.8,7.8g·kg-1,每天灌胃给药)对SHR收缩血压的影响。结果单次灌服养血清脑颗粒约1h,开始显示降压作用,2~3h达最高降压效果;连续给药2周后,高剂量组与模型组比较即有显著性差异(P<0.05);给药8周后,试验组与模型组比较均有显著性差异(P<0.05或P<0.01)。结论养血清脑颗粒有降低SHR收缩压的作用。     

重组人生长激素缓释微球.Ⅱ.大鼠体内的药物动力学研究

考察重组人生长激素（rhGH）可生物降解微球在动物体内的缓释效果，探讨蛋白稳定剂对微球体内药物动力学行为的影响。大鼠皮下注射rhGH-PLGA微球后，利用放射免疫吸附分析法测定血药浓度。结果表明，rhGH-PLGA微球具有明显的缓释作用，给药后d30，动物体内的rhGH浓度仍维持在正常生长激素水平之上。而大鼠同等剂量给予rhGH溶液24h后，其体内的生长激素浓度即恢复至正常水平。微球内水相中加入泊洛沙姆407（F127），使rhGH的相对生物利用度增加约12．5％，进一步证实了F127对rhGH具有稳定作用。     

杜仲叶提取物对清醒大鼠血压的影响

目的:观察杜仲叶提取物急慢性降压作用。方法:以间接测压法测量清醒大鼠尾动脉血压:(1)测量自发性高血压大鼠(SHR)多次灌胃杜仲叶提取物的血压变化,观察其慢性降压作用。(2)测量肾性高血压大鼠1次灌胃杜仲提取物后1,2,4,6,8h的血压,以观察提取物急性降压作用。结果:(1)连续18d灌胃杜仲叶提取物4.2g.kg-1或6.3g.kg-1均明显降低SHR血压。(2)一次性灌杜仲叶提取物4.2g.kg-1或6.3g.kg-1均明显降低肾性高血压大鼠血压。结论:杜仲叶提取物有明显的降低急慢性血压作用。     

甜菊苷对大鼠及犬的降血压作用

目的：评价甜菊苷的抗高血压作用。方法：采用动静脉插管术研究甜菊苷静脉注射对清醒及麻醉自发性高血压大鼠和麻醉犬的降血压作用特点。结果：清醒自发性高血压大鼠甜菊苷５０～２００ｍｇ／ｋｇ,ｉｖ,麻醉自发性高血压大鼠甜菊苷２５～３９８ｍｇ／ｋｇ,ｉｖ麻醉犬甜菊苷１６～１５９ｍｇ／ｋｇ,ｉｖ,均可剂量依赖地降低收缩压和舒张压,降压持续时间延长,且降舒张压的作用较收缩压明显。自发性高血压大鼠甜菊苷６３～２５１     

重组降血压肽缓释微球的制备与体外释放

目的采用复乳溶剂蒸发法制备重组降血压肽(rAHP)缓释微球。方法以聚乳酸(PLA)为缓释材料,利用正交设计优化微球制备的最佳工艺条件,并考察了微球的体外释药特性。结果微球制备的最优工艺为:油相中PLA的浓度为7.5%、初乳搅拌速度为900 r/min、内水相与油相体积比为1∶10,外水相聚乙烯醇124浓度为5%;按此工艺制备的微球粒径跨度小、分布均匀,包封率为81.35%,载药量在10.92%,微球得率在80.26%,微球的平均粒径分布范围在75～80μm之间;载药微球在磷酸盐缓冲液中0.5 h内的累积释药量为17.5%,第15天累积释药率达到98.6%。结论该微球制备工艺成熟,包封率高,符合我国药典对缓释制剂的指导原则要求。     

Effect of prolyl-leucyl-glycinamide on blood pressure, heart rate and angiotensin converting enzyme activity in spontaneously hypertensive and Wistar-Kyoto normotensive rats

The effect of melanotropin release inhibiting factor (L-prolyl-L-leucyl-glycinamide, MIF) on blood pressure and heart rate of both spontaneously hypertensive (SH) and age-matched normotensive Wistar-Kyoto (WKY) rats was investigated. A single s.c. injection of MIF at a lower dose (1 mg/kg) had no effect on the blood pressure of either SH or WKY rats when measured 1,4 and 7 hr after the injection of MIF. Higher doses of MIF (2 or 4 mg/kg), on the other hand, significantly depressed blood pressure in SH animals at 4 and 7 hr after the drug injection. However, MIF had no effect on the blood pressure of WKY rats. None of the doses of MIF had any appreciable effect on the heart rate of either SH or WKY rats. Angiotensin-converting enzyme (ACE) activity of anterior pituitary of WKY rats was significantly higher than that of SH rats. ACE activity of neurohypophysis, however, was lower in WKY rats than in SH rats. No change in the ACE activities of central and peripheral tissues (plasma, pituitary, striatum and hypothalamus) of SH rats was observed 4 hr after the administration of MIF (1, 2 or 4 mg/kg), a time at which MIF produced significant antihypertensive effect. It is concluded that MIF causes a delayed lowering of blood pressure only in the genetically hypertensive rats and that this effect is not mediated via an action on the ACE.     

PERTUSSIS TOXIN-SENSITIVE G-PROTEINS AND REGULATION OF BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. Increased Gi-protein-mediated receptor-effector coupling in the vasculature of the spontaneously hypertensive rat (SHR) has been proposed as a contributing factor in the maintenance of elevated blood pressure. If increased Gi-protein-mediated activity plays an important role in hypertension in SHR, then inhibition of Gi-proteins by pertussis toxin would be expected to decrease blood pressure in this genetic hypertensive model. To address this hypothesis, studies were undertaken comparing the cardiovascular effects of pertussis toxin in SHR and normotensive Wistar-Kyoto (WKY) rats. 2. Spontaneously hypertensive and WKY rats were instrumented with radiotelemetry devices and blood pressure measurements were recorded in conscious rats. Following a single injection of pertussis toxin (10 micrograms/kg, i.v.), mean arterial blood pressure fell from 161 +/- 3 to 146 +/- 1 mmHg in the SHR and the effect was sustained for more than 2 weeks. In contrast, 10 micrograms/kg, i.v., pertussis toxin produced no significant effect on blood pressure in WKY rats (103 +/- 4 vs 101 +/- 5 mmHg). 3. In a separate study, SHR and WKY rats were administered 30 micrograms/kg, i.v., pertussis toxin or 150 microL/kg, i.v., saline and, 3-5 days later, rats were anaesthetized and instrumented to permit measurement of blood pressure and renal function. At this higher dose, pertussis toxin reduced blood pressure in both strains of rat, although the effect was markedly greater in SHR (approximately 40 mmHg decrease) compared with WKY rats (approximately 15 mmHg decrease). In SHR, pertussis toxin increased renal blood flow (from 5.7 +/- 0.3 to 7.5 +/- 0.8 mL/min per g kidney) and decreased renal vascular resistance (from 31 +/- 2 to 19 +/- 2 mmHg/mL per min per g kidney). In WKY rats, pertussis toxin had no significant effect on renal parameters. 4. Results from these studies indicate that a pertussis toxin-sensitive Gi-protein-mediated pathway contributes to the maintenance of hypertension and elevated renal vascular tone in the SHR.     

The antihypertensive effect of a selective central muscarinic cholinergic antagonist: N-(4-diethylamino-2-butynyl)-succinimide

N-(4-Diethylamino-2-butynyl)-succinimide (DKJ-21), a cholinergic antagonist selective for muscarinic receptors in the central nervous system, has an antihypertensive effect in conscious spontaneously hypertensive rats (SHR) but not in normotensive Wistar-Kyoto (WKY) control rats. Intravenous doses over a range of 3.1 to 25.0 mg/kg produced a dose-dependent decrease in systolic blood pressure. This effect was still apparent 24 hr after drug administration, but blood pressure returned to predrug levels by 48 hr after injection of DKJ-21. In a dose–response study, the maximum antihypertensive response in a group receiving 25.0 mg/kg was 43 ± 8 mm Hg. Marked variability of the maximum response was observed in all age groups and with all doses. Decreases in blood pressure up to 75 mm Hg were obtained in individual animals. The magnitude of the antihypertensive effect is not age related since 10-, 15-, 22-, and 36-week-old SHR responded to the same degree after injection of 25 mg/kg DKJ-21. Smaller doses (50 μg) of DKJ-21 decreased blood pressure when administered into the lateral cerebral ventricle of SHR. Vascular responses to norepinephrine, acetylcholine, dimethylphenylpiperazinium, angiotensin I, and tyramine were not inhibited by i.v. injection of DKJ-21; however, the centrally mediated pressor response to physostigmine was reduced by 60%.     

Anti-hypertensive effects of probenecid via inhibition of the α-adrenergic receptor

Probenecid has long been used in the treatment of gout. Its anti-gout mechanisms consist of uric acid reuptake inhibition and the consequent facilitation of uric acid excretion. In the present study, we investigated whether probenecid could exert an anti-hypertensive effect in spontaneously hypertensive rats (SHR). The noninvasive indirect tail cuff method was employed to measure blood pressure and heart rate. The administration of probenecid (50 mg/kg, ip) induced a significant systolic blood pressure (SBP) decrease, from 167 mmHg to 141 mmHg, within 120 min. In contrast, probenecid had little effect on normotensive control Wistar Kyoto rats (WKY). The anti-hypertensive effects of probenecid are almost as potent as those of atenolol. In a further exploration of the anti-hypertensive mechanisms of probenecid, its effects on phenylephrine-induced blood vessel contraction were tested. Our results suggest that probenecid significantly inhibited the contractions of rat aorta. This effect was also observed with endothelium-removed rat aorta, suggesting that probenecid can directly interact with the α-adrenergic receptor. Moreover, probenecid inhibited the α-adrenergic-receptor-mediated activation of ERK I/II in MC3TC-E1 cells. Therefore, our results indicate that probenecid might alleviate high blood pressure in SHR via inhibition of the α-adrenergic receptor and ERK I/II.     

Effect of clonidine on renal sodium handling in spontaneously hypertensive rats

Up-regulation of kidney α2-adrenoceptor expression has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). This study was carried out to evaluate renal sodium excretion in response to clonidine administration in SHR and control normotensive Wistar-Kyoto (WKY) rats. SHR and WKY rats (12-week-old) were placed in metabolic cages for 4 days: the first 2 days in control conditions and the following 2 days under oral clonidine treatment (100 μg/kg body weight). Clonidine produced a similar reduction in systolic blood pressure values in SHR and WKY rats, although SHR remained hypertensive. At the end of the study SHR and WKY rats presented similar noradrenaline plasma levels. However, noradrenaline kidney tissue levels were significantly higher in SHR compared to WKY rats. Under control conditions, SHR presented lower urine flow compared to WKY rats. Clonidine produced a significant decrease in urine flow in WKY rats but not in SHR. Furthermore, clonidine also produced a significant reduction in urinary sodium, potassium, and creatinine excretion in WKY rats, but had no effect in SHR. In conclusion, in SHR the reduction in systolic blood pressure and sympathetic activity produced by clonidine was not accompanied by a decrease in urine volume and sodium excretion.     

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.     

人工合成胸腺素α1静脉注射或皮下注射在小鼠和大鼠体内的药动学研究

目的:研究人工合成胸腺素α1(sTα1)静脉注射或皮下注射在小鼠和大鼠体内的药动学特征。方法:取小鼠45只(sTα1,1mg·kg-1)、大鼠3只(sTα1,0.5mg·kg-1),尾静脉注射相应药物,分别于注射前及注射后6h内小鼠眼眶静脉采血和大鼠心脏采血;另取小鼠180只,随机分为高、中、低(sTα1,5、1、0.32mg·kg-1)剂量组,取大鼠9只,随机分为高、中、低(sTα1,2.5、0.5、0.16mg·kg-1)剂量组,皮下注射相应药物,分别于注射前及注射后10h内小鼠眼眶静脉采血和大鼠心脏采血,用酶联免疫吸附法检测各时间点的血药浓度,并计算其药动学参数。结果:sTα1静脉注射在小鼠体内的t1/2β为0.68h、AUC0～∞为554.32μg·h·L-1,在大鼠体内的t1/2β为(1.87±0.50)h、AUC0～∞为(1602.91±360.41)μg·h·L-1;sTα1高、中、低剂量组皮下注射在小鼠体内的t1/2分别为0.76、0.54、0.268h,AUC0～∞分别为3222.95、417.67、366.60μg·h·L-1,在大鼠体内的t1/2分别为(1.23±0.23)、(1.40±0.37)、(1.99±0.94)h,AUC0～∞分别为(22436.74±5641.94)、(1539.63±203.30)、(729.60±320.0)μg·h·L-1。结论:sTα1在大鼠和小鼠体内静脉注射的药动学过程属于一级二室开放模型,皮下注射的药动学过程属于一级一室开放模型。     

Effect of tissue norepinephrine depletion by 6-hydroxydopamine on blood pressure in spontaneously hypertensive rats

Blood pressure was studied in normotensive and spontaneously hypertensive rats (SHR) in which catecholamine depletion had been produced by 6-hydroxydopamine. After i.v. administration of 80–200 mg/kg 6-hydroxydopamine, norepinephrine (NE) levels in heart, spleen, and kidney were markedly reduced (14–66% of control value) while brain NE remained unchanged. These doses did not affect development of hypertension in SHR or the blood pressure in normotensive control rats during a 20 day period of study. A transient decrease of blood pressure was observed acutely (1–3 days) after an 80 mg/kg dose in normotensive and hypertensive animals. Depletion of NE in the brainstem (to 33–42% of control value) after intraventricular injection of 6-hydroxydopamine, 50–300 μg, had no effect on blood pressure of SHR and normotensive rats. It is concluded that only a small portion of tissue NE content is sufficient for development and maintenance of hypertension in the SHR.     

鸡血藤醇提物对血虚模型小鼠的补血作用

目的:研究鸡血藤醇提物对血虚模型小鼠的补血作用。方法:通过放血以复制小鼠失血性血虚模型;通过腹腔注射环磷酰胺(25 mg/kg)以复制小鼠化学性血虚模型;通过皮下注射乙酰苯肼(20 mg/kg)同时控制饮食以复制小鼠综合血虚模型。60只KM种小鼠随机分为正常对照(等体积生理盐水)组、模型(等体积生理盐水)组、乌鸡白凤丸(4 g/kg)组与鸡血藤醇提物高、中、低剂量(30、15、7.5 g/kg)组。制备模型的同时灌胃给药,每天1次,连续10 d。测定小鼠红细胞计数(RBC)、血红蛋白(HGB)、红细胞压积(HCT)、血小板计数(PLT)。结果:与正常对照组比较,模型组小鼠RBC、HGB、HCT、PLT降低,差异具有统计学意义(P<0.01)。与模型组比较,鸡血藤醇提物高、中、低剂量组小鼠RBC、HGB升高,差异具有统计学意义(P<0.01或P<0.05);鸡血藤醇提物高、中剂量组小鼠HCT、PLT升高,差异具有统计学意义(P<0.01或P<0.05)。结论:鸡血藤醇提物对血虚模型小鼠有良好的补血作用,其机制可能与调节血液系统有关。