柠檬总提取物对正常大鼠及SHR血压、血脂影响的实验研究

目的:研究安岳柠檬总提取物对正常及自发性高血压大鼠(SHR)血压、血脂水平的影响.方法:柠檬总提取物6.0 g·kg-1、3.6g·kg-1、2.16 g·kg-1连续灌胃给药21 d,颈动脉插管法观察对正常大鼠血压的影响,测定血清葡萄糖(GLU)、甘油三酯(TG)、血清总胆固醇(TC)含量;连续灌胃给药28 d,分别于给药7、14、21、28 d无创法测定SHR的血压,测定给药28 d后血清GLU、TG、TC含量.结果:柠檬总提取物6.0 g·kg-1对正常麻醉大鼠具有降血压作用,但对SHR血压无显著影响;各剂量组对正常大鼠、SHR血清TG含量有显著降低作用.结论:柠檬总提取物具有明确的降低TG含量作用,改善血脂代谢;其降血压作用的发挥可能与给药途径有关,有待进一步验证.     

萘哌地尔衍生物BWYJ对大鼠血压及猫血流动力学的影响

目的:观察萘哌地尔衍生物BWYJ对高血压模型和正常大鼠血压及猫血流动力学的影响。方法:分别对高血压和正常大鼠静脉及灌胃给药,观察血压变化;利用麻醉开胸测定猫血流动力学的变化;采用侧脑室给药、猫在体瞬膜神经肌肉标本初步探讨降压机制。结果:BWYJ1.2及2.4mg·kg-1iv,降低正常及高血压大鼠收缩压(SAP)和舒张压(DAP),且随剂量的增加效应增加,作用时间延长。BWYJ10、20及40mg·kg-1灌胃给药,降低清醒正常大鼠SAP(最大效应分别下降4.6%、13.0%、16.8%)和DAP(分别下降7.1%、17.9%、20.5%),3h后恢复。BWYJ5、10及20mg·kg-1灌胃清醒高血压大鼠,降低SAP(下降7.3%、16.5%、20.4%)和DAP(8.5%、14.8%、24.5%),强于正常大鼠且时间明显延长。麻醉猫十二直肠给药,BWYJ2.5mg·kg-1仅DAP、LVWI降低,BWYJ5mg·kg-1使SAP、DAP、TPR、±dp/dtmax及LVWI明显降低,其他无明显变化。结论:BWYJ静脉或灌胃给药对正常和肾性高血压大鼠产生降压作用,降压作用与中枢、神经节无关。     

Effect of cross-fostering on blood pressure and renal function in the New Zealand genetically hypertensive rat

1. The severity of hypertension displayed by adult spontaneously hypertensive rats (SHR) and Dahl (SS/Jr) rats can be reduced by 20-30 mmHg if the hypertensive pup is cross-fostered to a normotensive mother within the first 2 weeks of birth. In the SHR, at least, this blood pressure-lowering effect arises through programming of the neonatal kidney to excrete sodium more effectively. Thus, cross-fostering may only be effective in lowering pressure in salt-sensitive hypertensive strains. Accordingly, the aim of the present study was to determine whether cross-fostering is effective in lowering adult blood pressure in the salt-resistant New Zealand genetically hypertensive (GH) rat. 2. Genetically hypertensive and control normotensive (N) rat pups were reared by either their natural mothers or a foster mother of the opposite strain (NX and GHX). Blood pressure was tracked from the age of 6-18 weeks, at which time renal function was assessed using standard clearance techniques in anaesthetized rats. Renal function was also assessed in a separate group of young rats at 5-6 weeks of age. 3. Cross-fostered GHX rats had lower blood pressure than GH rats, but this difference was only apparent until 9 weeks. The NX rats had higher blood pressures than N rats, but again pressure converged at 10 weeks. Basal renal function did not differ between GH and GHX rats or between N and NX rats at either age. However, young GH rats had lower renal blood flow, glomerular filtration rate, urine output and sodium excretion than N rats. 4. These data show that cross-fostering is effective in lowering blood pressure in GH rats, albeit transiently. The kidneys do not appear to play a role, because renal function did not differ under the current experimental conditions between GH and GHX rats. However, the kidney may play a greater role in the onset of hypertension in the GH rat than previously thought.     

Beneficial effects of the combination of amlodipine and losartan for lowering blood pressure in spontaneously hypertensive rats

A combination of antihypertensive agents can better control blood pressure and reduce the number and severity of side effects than a monotherapy. Since both CCBs (calcium channel blockers) and ARBs (angiotensin II receptor type-1 blockers) are current and effective antihypertensive drugs, this study assessed the synergistic antihypertensive effects as well as the optimal combination ratio of these two drugs. Amlodipine (3 mg/kg) or losartan (30 mg/kg) alone or a combination of each drug at a ratio 1:10 and 1:20 was administered orally to spontaneously hypertensive rats (SHR). A four-week treatment of either 3 mg/kg amlodipine or 30 mg/kg losartan alone decreased the systolic blood pressure (SBP). However, their combination significantly lowered the SBP from the 3^rd week, and there was a positive correlation between this reduction in blood pressure and the improvement in arterial endothelium-dependent relaxation. In addition, the combination therapy (1:20) decreased both the cardiac mass and left ventricular weight to a greater extent than with either amlodipine or losartan alone. The collagen content in the cardiac tissue was also significantly lower after the 4-week combination therapy (1:10). These results suggest that the combined use of amlodipine and losartan might be more effective in treating hypertension than a monotherapy.     

Effect of simvastatin given alone and in combination with valsartan or enalapril on blood pressure and the structure of mesenteric resistance arteries and the basilar artery in the genetically hypertensive rat model

1. The aims of the present study were to investigate, in the New Zealand genetically hypertensive (GH) rat model, the effects of treatment with simvastatin, alone or in combination with valsartan or enalapril, on blood pressure (BP) and structural remodelling of mesenteric resistance arteries (MRA) and of the basilar artery, an artery that plays a major role in the regulation of cerebral resistance. 2. Genetically hypertensive rats were treated with simvastatin at two dose levels (5 and 10 mg/kg per day) and simvastatin in combination with valsartan or enalapril (also 5 and 10 mg/kg per day) from the age of 7 to 12 weeks. Systolic BP and bodyweight were measured weekly. 3. At the end of the experiment, following fixation by perfusion, MRA and the basilar artery were excised and embedded in Technovit (a glycol methacrylate medium; Heraeus Kulzer, Werheim, Germany). Serial sections were cut and stereological techniques used to determine tunica media width and cross-sectional area (CSA), lumen diameter and the ratio of media width/lumen diameter. 4. Simvastatin monotherapy did not lower BP at either dose. In the high- and low-dose groups, the combination of simvastatin + enalapril lowered BP more than with enalapril alone; this was also true for the simvastatin + valsartan combination in the lower-dose group. 5. The MRA were hypotrophically remodelled by the 10 mg/kg per day dose of simvastatin; the 5 mg/kg per day dose caused hypotrophic remodelling with decreased media/lumen ratio. Valsartan and enalapril caused hypotrophic remodelling together with outward remodelling of the lumen in the 10 mg/kg per day valsartan group and, in all groups, a reduction in the media/lumen ratio, with the greatest effect observed in the high-dose groups. 6. The combination treatments of simvastatin + valsartan and simvastatin + enalapril did not have any consistent extra effect on MRA remodelling. 7. In the basilar artery, high-dose simvastatin had a hypotrophic effect on the media and both doses reduced the media/lumen ratio independently of any change in BP. 8. Simvastatin given in combination with valsartan produced a slight further reduction in medial CSA, media width and ratio. In combination with enalapril, there was little consistent additional effect. 9. Simvastatin monotherapy hypotrophically remodelled the media of the basilar artery in the GH rat model, even in the absence of changes in BP. A similar structural effect may explain, in part, the reduction in stroke seen in patients treated with statins.     

多沙唑嗪对映体对大鼠血压和排尿功能的影响

目的观察十二指肠给予多沙唑嗪(rac-DOX)及其对映体(S-DOX、R-DOX)对麻醉大鼠血压和膀胱排尿功能的影响。方法采用八道生理仪记录麻醉大鼠颈总动脉血压、心率以及膀胱排尿压、排尿间隔,并测量排尿量。结果十二指肠给予S-DOX、R-DOX和rac-DOX均可剂量依赖性降低颈总动脉收缩压、舒张压和平均动脉压,1.0mg.kg-1时3者对平均动脉压的降低幅度分别达到23.5%±4.6%、38.5%±8.9%和42.6%±7.5%,3者降低平均动脉压的ED30值依次为(2.0±0.8)、(0.6±0.7)、(0.6±0.5)mg.kg-1。S-DOX降低收缩压、舒张压和平均动脉压的作用均弱于rac-DOX和R-DOX(P<0.05),rac-DOX与R-DOX的降压作用差异无显著性(P>0.05)。rac-DOX在0.1～3.0mg.kg-1剂量范围内剂量依赖性抑制麻醉大鼠心率,而S-DOX和R-DOX仅在3.0mg.kg-1剂量时对心率有抑制作用。十二指肠给予S-DOX、R-DOX和rac-DOX均剂量依赖性降低麻醉大鼠膀胱排尿压,3种药物对排尿压的最大降低幅度分别为13.4%±5.7%、14.5%±11.0%和10.9%±7.6%,3者降低排尿压的作用差异无显著性(P>0.05)。与S-DOX相比,R-DOX可缩短排尿间隔并减少排尿量(P<0.05),而S-DOX和rac-DOX对排尿间隔和排尿量无影响。结论与R-DOX和rac-DOX相比,S-DOX保留了对麻醉大鼠膀胱排尿压的有利作用,减轻了对血压、心率和膀胱排尿间隔的不良影响。     

Release of endogenous GABA in the posterior hypothalamus of the conscious rat; effects of drugs and experimentally induced blood pressure changes

Summary Push-pull superfusion was used to investigate the release of endogenous GABA in the posterior hypothalamus of the conscious, freely moving rat at basal conditions and in response to centrally applied drugs or to peripherally induced blood pressure changes.After an initial, exponential decline, the release rate of GABA remained fairly constant for many hours. Fluctuations in the release rate of GABA point to the existence of an ultradian rhythm with an approximate frequency of 1 cycle/65 min. Hypothalamic superfusion with a potassium-rich (50 or 90 mmol/1) artificial cerebrospinal fluid led to a concentration-dependent increase in the GABA release. The release of GABA was also enhanced by veratridine (1 or 10 mol/1) in a concentration-dependent way. Hypothalamic superfusion with the neutrotoxin tetrodotoxin (1 gmmol/1) led to a long-lasting decrease in the GABA release. The rise in blood pressure (45 mmHg) elicited by an intravenous infusion of noradrenaline was associated with an increased release rate of GABA in the hypothalamus. Hypotension produced by nitroprusside (25 mmHg) led to a counteracting decrease in hypothalamic GABA outflow.The findings suggest that approximately 4510 of the basal outflow of GABA found in the superfusate are released from GABA-ergic neurons of the posterior hypothalamus. The release rate of GABA fluctuates according to an ultradian rhythm. The modified release of GABA in response to experimentally induced blood pressure changes suggests that, in the posterior hypothalamus of the conscious rat, GABAergic neurons are involved in cardiovascular control and possess a hypotensive function.This work was supported by the Fonds zur Förderung der wissenschaftlichen ForschungCorrespondence to N. Singewald at the above address     

Analysis of the action of tyramine on blood pressure in the rat

In urethane anaesthetized rats, tyramine, 1 mg/kg, i.v. produced a considerable rise in blood pressure. In rats pretreated with reserpine, 10 mg/kg, injected i.p. 16–24 hr before, the pressor response was still quite large.The residual response after reserpinization was almost abolished by adrenalectomy or by pithing. The findings suggest that the pressor action of tyramine in the rat is due in part to a central or centrally mediated stimulation of the nerve supply to the adrenal medulla.     

柳珊瑚酸与N-环己基柳珊瑚酰胺对大鼠和猫尿量、呼吸和血压的影响(英文)

目的:比较柳珊瑚酸(suberogorgin,Sub)与N-环己基柳珊瑚酰胺(N-cyclohexyl suberogorgamide,N-CS)的药理作用。方法:大鼠和麻醉猫给予水负荷和Sub或N-CS后记录其尿量,并测定尿Na~ ,K~ 浓度;猫实验中Sub和N-CS采用等毒性剂量(1/50 LD_(50))。结果:Sub 0.4 mg·kg(-1)和N-CS 1.5mg·kg~(-1)iv分别使猫尿量减少63％和增加25％,这种作用维持9h以上。Sub和N-CS均明显提高猫呼吸频率和潮气量,但对血压无明显影响。Sub 1.3mg·kg~(-1)和N-CS 3.2mg·kg~(-1)ip分别使大鼠尿量减少48％和增加14％,并有明显的排Na~ ,K~ 作用。结论:Sub具抗利尿作用而N-CS却具利尿利用。     

尼群地平和卡托普利协同降低去窦弓神经大鼠血压波动性的作用

目的研究联合应用尼群地平和卡托普利可能具有的协同降低去窦弓神经大鼠血压及血压波动性的作用。方法以去窦弓神经大鼠为模型分别测定单次给予尼群地平或卡托普利及尼群地平与卡托普利联合应用后清醒自由活动大鼠的动脉血压、心动周期、血压波动性及心动周期波动性;采用概率和法计算尼群地平和卡托普利联合应用后对大鼠血压及血压波动性的作用。结果单用尼群地平5mg.kg-1或卡托普利100mg.kg-1能明显降低去窦弓神经大鼠的收缩压和舒张压,两药合用后降压作用明显加强,计算所得q值分别为1.23和1.38;单用尼群地平能显著降低去窦弓神经大鼠的收缩压波动性和舒张压波动性,单用卡托普利后对去窦弓神经大鼠的收缩压波动性和舒张压波动性没有明显影响,两药合用后可以显著降低大鼠的收缩压和舒张压波动性,q值分别为1.20和1.38;尼群地平和卡托普利无论是单用还是合用对去窦弓神经大鼠的心率及心率波动性都没有显著影响。结论尼群地平和卡托普利联合应用后具有协同降低和稳定去窦弓神经大鼠血压及血压波动性的作用。     

有机铬对实验性糖尿病大鼠降血糖作用的观察

目的 :观察有机铬对实验性糖尿病大鼠的降血糖作用。方法 :用葡萄糖氧化酶法观察了口服有机铬 4 0 0μg/ kg.d及80 0μg/ kg.d连续 84 d的四氧嘧啶所致糖尿病大鼠血糖水平。结果 :每日 80 0μg/ kg体重组和 4 0 0μg/ kg体重组血糖与糖尿病模型组相比较均有明显下降 ,有显著性差异 (P <0 .0 5 )。每日 80 0μg/ kg体重组血糖浓度虽仍比正常组高 ,但已无显著差异(P>0 .0 5 ) ,每日 4 0 0μg/ kg体重组血糖浓度虽比糖尿病模型组有明显下降但与正常组相比较仍有显著性差异 (P >0 .0 5 )。结论 :有机铬可明显降低实验性糖尿病大鼠血糖水平     

组胺对离体兔中枢和外周血管收缩作用的比较及其机理初探

目的：比较组胺及其受体阻断药对离体家兔脑及外周血管的作用；并观察钙离子在组胺效应机制中的作用。方法：取家兔基底动脉和肠系膜动脉，分别在不同剂量苯海拉明、西咪替丁和硝苯地平存在的情况下，观察组胺量效曲线的变化。结果：组胺可引起基底动脉和肠系膜动脉收缩；苯海拉明可拮抗组胺的上述作用；西咪替丁小剂量时即可增强组胺所致的基底动脉的收缩，而大剂量时才对组胺引起的肠系膜动态心缩有增强作用；硝苯地平对组胺引起的两种动脉的收缩都有抑制作用。结论：组胺对离体家兔脑及外周血管均有收缩作用。这种缩血管作用主要通过Ca^2 内流引起。同时，实验结果提示两种血管上组胺受体的分布密度有差别。     

Protective effects of quercetin on ultraviolet A light-induced oxidative stress in the blood of rat

The oxidative effects of ultraviolet A (UVA) light (320-400 nm) and the antioxidant effects of quercetin were examined in rat blood. For this purpose, rats were divided into three groups: control, ultraviolet (UV) and ultraviolet + quercetin (UV + Q). The UV and UV + Q groups were irradiated for 4 h a day with UVA light (1.25 mW cm(2)) during periods of 3, 6 and 9 days. Quercetin (50 mg kg(-1) body wt.) was administered intraperitoneally in the UV + Q group rats before irradiation periods. Blood was taken 3, 6 and 9 days post-treatment. Plasma malondialdehyde (MDA) levels significantly increased after 9 days of daily exposure to UVA. Whole blood glutathione (GSH) levels significantly declined after 3-9 days of irradiation. Glutathione peroxidase activity on days 6 and 9 and glutathione reductase activities on days 3, 6 and 9 post-irradiation were diminished significantly. Superoxide dismutase and catalase activities decreased significantly 3-9 days post-irradiation. The administration of quercetin before the 9-day period of irradiation significantly reduced the increase in plasma MDA value. Whole blood GSH levels significantly decreased with the administration of quercetin on all days. Quercetin significantly increased antioxidant enzymes diminished by UVA irradiation. Exposure of rats to UVA light leads to oxidative stress, reflected by increased MDA and reduced antioxidant enzyme levels. The administration of quercetin appears to be a useful approach to reduce the damage produced by UVA radiation.     

Ethylketocyclazocine decreases noradrenaline release and blood pressure in the rabbit at a peripheral opioid receptor

Summary Rabbits were pithed and their sympathetic outflow was stimulated electrically via the pithing rod. Arterial blood pressure, heart rate, the endogenous plasma noradrenaline level, the plasma ³H-noradrenaline clearance and the noradrenaline release rate (the rate of entry of endogenous noradrenaline into the plasma) were determined. Ethylketocyclazocine 0.1 mg kg^–1+0.02 mg kg^–1 h^–1 and 1 mg kg^–1 + 0.2 mg kg^–1 h^–1 but not 0.01 mg kg^–1+ 0.002 mg kg^–1 h^–1 decreased blood pressure, the endogenous plasma noradrenaline level and the noradrenaline release rate. The effects of ethylketocyclazocine 1 mg kg^–1+ 0.2 mg kg^–1 h^–1 were antagonized by naloxone 1 mg kg^–1 + 0.5 mg kg^–1 h^–1. Given alone, naloxone caused no change. It is concluded that ethylketocyclazocine inhibits action potential-evoked release of noradrenaline from postganglionic sympathetic neurones, and hence can lower blood pressure, by a peripheral effect, possibly mediated by opioid receptors at the terminal axons.     

阿魏酸钠对离体大鼠心脏的药理性预适应保护作用及机制

目的研究阿魏酸钠(sodiumferulate,SF)诱导药理性预适应对离体大鼠心脏的保护作用及其机制。方法将大鼠离体心脏随机分5组:正常组(Control组,富氧液灌注100min);缺氧/复氧损伤组(I/R组,稳定灌流30min,缺血停灌40min后复灌30min);缺血预适应组(IP组,行3次停灌5min、复灌5min刺激后,停灌40min、复灌30min);SF组(用含有1.69mmol.L-1SF的灌流液灌流15min后改用正常灌流液灌流15min,后行停灌40min、复灌30min);格列本脲组(Gli组,用格列本脲30μmol.L-1和SF1.69mmol.L-1合用灌流心脏15min后改用正常灌流液灌流15min,后行停灌40min、复灌30min)。结果与I/R组相比1.69mmol.L-1SF能明显改善心功能、减少心律失常发生率及严重程度、降低心肌组织钙超载、保护心肌Na+,K+-ATP酶、Ca2+ATP酶活性。30μmol.L-1格列本脲与SF合并使用后,上述心肌保护作用则部分取消。结论SF预处理能改善心功能,抗心律失常、抗钙超负荷,其作用机制至少部分与KATP通道开放有关。     

缬沙坦与贝那普利对原发性高血压患者运动血压的影响

目的：探讨血管紧张素受体拮抗剂缬沙坦及转换酶抑制剂贝那普利对原发性高血压患者运动血压的影响，为选择抗高血压的药物提供依据。方法：选择144例原发性高血压患者，分别在用药前及用药后进行运动平板试验，并取运动中最高收缩压及舒张压分别进行比较。结果：使用药物治疗至静息血压正常后，各组间运动血压的下降值差异无显著性。同时，有部分患者仍存在运动高血压的情况。结论：缬沙坦与贝那普利均能使高血压患者的运动血压下降，但二者联合使用并不能使高血压患者的运动血压进一步降低。     

生脉类制剂调节血压作用的药理与临床研究概述

生脉类制剂是在古方生脉散的基础上,引入现代技术制成的成药制剂,主要有生脉饮、生脉胶囊、生脉注射液、注射用益气复脉（冻干）等。生脉类制剂具有改善心脏功能、保护心肌细胞以及改善微循环等作用,广泛应用于心脑血管类疾病,近年来有关生脉类制剂对血压双向调节作用（升压和降压）的研究有大量报道。对生脉类制剂调节血压的相关药理及临床研究进行综述,以期为该类制剂调节血压的理论研究和临床应用提供参考。     

Effects of glitazones on blood pressure and vascular structure in mesenteric resistance arteries and basilar artery from genetically hypertensive rats

1. The effects of two of the glitazone (thiazolidinedione) class of drugs, namely rosiglitazone and pioglitazone, on blood pressure and vascular remodelling in the New Zealand genetically hypertensive (GH) rat model were investigated. 2. In the first study, a GH group given rosiglitazone (5 mg/kg per day) from the age of 7 to 12 weeks was compared with a GH control group. In the second study, GH rats were given either pioglitazone, simvastatin, valsartan or combinations of pioglitazone with simvastatin or valsartan (all drugs at a dose of 10 mg/kg per day). 3. Tail-cuff systolic blood pressure was measured weekly. At the end of the experiment, blood vessels were fixed by perfusion and samples of mesenteric resistance arteries (MRA), second-order branches and basilar artery were embedded in Technovit and serial sections were cut and stained with Giemsa for stereological analysis. Media width, medial cross-sectional area and lumen diameter were determined and the ratio of media width/lumen diameter was calculated. 4. Rosiglitazone significantly reduced blood pressure in GH rats. 5. In MRA, rosiglitazone had a hypotrophic effect on media, reduced lumen diameter and reduced media/lumen ratio (P<0.001). 6. In basilar artery, there was also a hypotrophic effect of rosiglitazone on media and reduced media/lumen ratio (P<0.001). 7. Pioglitazone slowed down the rate of blood pressure increase with age in GH rats and had a greater effect on blood pressure when given in combination with simvastatin. 8. Pioglitazone had a hypotrophic effect on the media of MRA and basilar artery. The hypotrophic effect was enhanced when pioglitazone was given in combination with simvastatin. The media/lumen ratio was reduced by pioglitazone; in MRA, combination treatment with simvastatin reduced the ratio further to normal and, with valsartan, to below normal. In basilar artery, the media/lumen ratio was reduced further by both combination treatments, but was lowest in the pioglitazone-valsartan combination group. 9. The significant effects on MRA and basilar artery structure (and, thus, haemodynamics) seen after rosiglitazone monotherapy and after pioglitazone, given alone and in combination with simvastatin or valsartan, may well indicate a glitazone class effect on vascular structure and, hence, cardiovascular function.     

高血压患者血压水平和脉压与脑卒中的关系

目的:探讨原发性高血压病不同收缩压、舒张压、脉压水平与脑卒中发生率的关系。方法:收集原发性高血压患者186例,其中单纯并发脑卒中者84例。按收缩压、舒张压、脉压的水平不同分别分为四组,观察各组脑卒中的发病率。结果:随着收缩压、舒张压、脉压水平的增高,脑卒中的发病率增加,P<0.05,有统计学意义。结论:在我国脑卒中是人群主要的病残和死亡原因。积极有效地降低血压水平及脉压差,是防治脑卒中的重要环节。