左旋千金藤立定的降压作用分析

麻醉犬、大鼠、兔,静脉注射或十二指肠注射SPD均有降压作用。SPD对犬颈总动脉升压反射及刺激迷走神经、坐骨神经升压反射都呈抑制。犬第四脑室及毁脊髓大鼠注射SPD均可降压。这表明SPD降压存在中枢和外周作用部位,外周可能更重要,血管α受体可能是SPD降压的主要机理之一。     

左旋千金藤立定对大鼠血清中催乳素水平的影响

目的：观察左旋千金藤立定（ＳＰＤ）对血清催乳素（ＰＲＬ）水平的影响，研究ＳＰＤ的药理作用，方法：成熟♀鼠ｉｐ多巴胺受体激动剂，拮抗剂或ＳＰＤ后断头取血，然后用放射免疫法测定血清中的催乳素水平。结果：ＳＰＤ引起血清ＰＲＬ水平迅速而显著的增增加，效应持续效约１ｈ，具有剂量依赖性，ＳＰＤ的半数有效剂量为３．７ｍｇ．ｋｇ＾－１（９５％可信限为２．６－４．３ｍｇ．ｋｇ＾－１）剂量为２０ｍｇ．ｋｇ＾－１时产生     

左旋千金藤立定对大鼠脑缺血再灌注损伤的保护作用

观察左旋千金藤立定 (SPD)对大鼠脑缺血再灌注损伤的保护作用 .大鼠两侧椎动脉凝闭 4 - 5h后 ,夹闭 30min颈总动脉 ,再灌注 90min ,大鼠脑含水量 ,钠和丙二醛 (MDA)含量较对照组明显增高 ,而超氧化物歧化酶 (SOD)活力较对照组降低 ,并伴有脑电图异常和脑组织结构病理变化 .夹闭颈总动脉前 30minipSPD 5～ 10mg·kg- 1,降低脑组织水 ,钠和MDA含量 ,并提高SOD活力 .组织学检查及脑电图也有所改善 .提示SPD有一定的保护脑缺血再灌损伤作用 .     

左旋千金藤立定对大鼠纹状体缺血性损伤的拮抗作用

AIM: To elucidate the protection of l-stepholidine (SPD) on neuronal morphology and function against the striatal ischemic injury in rat. METHODS: The forebrain ishemia to Sprague Dawley rats was induced with four-vessel occlusion. Histological examination was performed on the dorsolateral striatum with cresylviolet stain. In striatal slices of rat as an in vitro ischemic model, the activity of calcium/calmodulin-dependent protein kinase II (CCDPK) and lactate dehydrogenase (LDH) was examined by the method of 32P-incorporation and colorimetry, respectively. RESULTS: In the SPD-treated groups, most of the neurons in the striatum kept the normal morphological appearance after 30-min ischemia followed by 6-h or 12-h reperfusion. The number of neurons was much more in SPD groups than that in vehicle group. The sparse and abnormal neurons were observed in the vehicle group. SPD attenuated the ischemic effect on the CCDPK activity in striatal slices. In addition, SPD inhibited the leakage of LDH from neurons induced by ischemia in incubated striatal slices. CONCLUSION: SPD protected striatal neurons against ischemic injury and antagonized the inhibitory action on CCDPK activity induced by ischemia. SPD reduced the leakage of LDH from striatal neurons induced by ischemia.     

左旋千金藤立定加强尾核脑片多巴胺释放

观察左旋千金藤立定对家兔尾核脑片多巴胺释放的影响。以［＾３Ｈ］ＤＡ预孵脑片，测定ＤＡ放射性。选择性Ｄ２受体激动剂ＬＹ１７１５５５以剂量依赖方式抑制电诱发的兔尾核脑片［＾３Ｈ］ＤＡ释放。     

左旋千金藤啶碱对外周血管多巴胺DA_1和DA_2受体亚型的作用

用家兔离体血管环方法，研究左旋千金藤啶碱（ｌＳＰＤ）对外周血管ＤＡ１和ＤＡ２受体亚型的作用。结果表明，ｌＳＰＤ使ＤＡ１受体激动剂ＦＯＤＡ诱发的肾、肺和肠动脉以及ＤＡ２受体激动剂ＰＢＤＡ诱发的肠和股动脉舒张反应的量效曲线非平行右移，最大反应（Ｅｍａｘ）降低，均呈非竞争性拮抗；ｌＳＰＤ本身还可使肾和肺血管产生轻度的浓度依赖性舒张反应，表现为ＤＡ１受体激动剂的作用特性。提示ｌＳＰＤ为外周血管ＤＡ１和ＤＡ２受体的混合性阻滞剂并兼有ＤＡ１受体部分激动剂的双重作用特性。     

四氢原小檗碱类药物对培养大鼠单个心肌细胞内游离Ca2+的影响

用Fura-2/AM技术和AR-CM-MIC阳离子测定系统,直接测定了四氢小檗碱(tetrahy-droberberine,THB)、左旋四氢巴马汀(l-tetrahydropalmatine,THP)和左旋千金藤立定(l-stepholidine,SPO)对培养大鼠单个心室肌细胞内游离钙([Ca²⁺]i)的影响,并与维拉帕米(Ver)做了比较。结果显示,THB,THP,SPD浓度为10～100μmol·L^-1时,均可使静息[Ca²⁺]i轻度升高,河豚毒素不能抑制之;浓度为1～100μmol·L^-1时,可明显抑制高K+引起的[Ca²⁺]i增高;30μmol·L^-1对胞外高Ca²⁺和去甲肾上腺素引起的[Ca²⁺]i增高也有明显的抑制作用,但均较Ver的抑制作用为弱;THPB对哇巴因引起的[ca²⁺]i升高无明显抑制作用。结果提示,THB,THP,SPD在抑制电压依赖性钙通道从而影响细胞膜[ca²⁺]i内流方面与Ver相似,但比Ver弱。     

千金藤啶碱对大鼠脑内单胺代谢的影响

1-千金藤啶碱(1-SPD 15～120 mg/kg)能增加大鼠纹状体和边缘区的多巴胺代谢物DOPAC和HVA(+150～300%),并有剂量相关关系。此作用于给药后60 min达峰值,给药后4 h虽有恢复趋势,但仍明显高于对照值。SPD还能中等度地降低上述两个脑区的DA和NA(-18～48%)。DA转换率(表现为代谢物增加)的升高支持SPD为DA受体阻断剂。但DA和NA下降表明,除有受体阻断作用外,不能排除药物对单胺递质的贮存、释放或再摄取的影响。纹状体内的5-HIAA含量亦有明显升高。     

千金藤啶碱对大鼠脑内单胺代谢的影响

1-千金藤啶碱(1-SPD 15～120 mg/kg)能增加大鼠纹状体和边缘区的多巴胺代谢物DOPAC和HVA(+150～300%),并有剂量相关关系。此作用于给药后60 min达峰值,给药后4 h虽有恢复趋势,但仍明显高于对照值。SPD还能中等度地降低上述两个脑区的DA和NA(-18～48%)。DA转换率(表现为代谢物增加)的升高支持SPD为DA受体阻断剂。但DA和NA下降表明,除有受体阻断作用外,不能排除药物对单胺递质的贮存、释放或再摄取的影响。纹状体内的5-HIAA含量亦有明显升高。     

EFFECTS OF ENDOTHELIUM-DERIVED RELAXING FACTOR ON THE SMOOTH MUSCLE OF THE RAT TAIL ARTERY

Simultaneous measurements of smooth muscle membrane potential and tension were made from isolated pieces of rat tail artery. A single electrical stimulus to the perivascular nerves produced a transient contraction of the smooth muscle. The amplitude of the contraction was increased after removal of the endothelium. The excitatory junction potentials and action potentials in the smooth muscle had the same amplitudes before and after removal of the endothelium. Tension obtained by direct stimulation of the arterial muscle in guanethidine-treated arteries was also increased by removal of the endothelium. When the artery was constricted by noradrenaline or 5-hydroxytryptamine, electrical stimulation caused a relaxation that was reduced by removing the endothelium. It was concluded that the electrical stimulus released the endothelium-derived relaxing factor (EDRF) which reduced the amount of contractile force that could be produced by an action potential in the smooth muscle.     

EFFECTS OF NITRO-l-ARGININE ON ENDOTHELIUM-DEPENDENT RELAXATION OF CANINE CEREBRAL ARTERIES

1. The effect of N^G-nitro-l-arginine (NO₂Arg) on the relaxation of canine basilar artery was investigated and compared with those of middle cerebral and femoral arteries. 2. NO₂Arg (10^?7-3 × 10^?5 mol/L) inhibited the substance-P (Sub-P; 10^?12-10^?8 mol/L) induced relaxation in the basilar artery precontracted with prostaglandin F_2α (PGF_2α; 10^?5 mol/L) or KCl (10^?2 mol/L) in a concentration-dependent manner and a ratio of the maximum inhibition by NO₂Arg (3 × 10^?5 mol/L) was more than 90%. 3. The relaxation induced by A23187 (10^?9-3 × 10^?6) was also abolished by NO₂Arg (3 × 10^?5 mol/L), but that by glyceryl trinitrate (GTN; 10^?9-3 × 10^?5 mol/L) was not, in the basilar artery precontracted with PGF_2α (10^?5 mol/L). N^G-nitro-d-arginine (NO₂ArgD; 3 × 10^?5 mol/L) did not affect the relaxation induced by Sub-P (10^?12-10^?8 mol/L). 4. l-arginine (l-Arg; 3 × 10^?5-10^?4 mol/L) did not inhibit Sub-P (10^?12-10^?8 mol/L) induced relaxation in the basilar artery. Pretreatment of l-Arg (10^?4 mol/L) reversed the relaxation inhibited by NO₂Arg (3 × 10^?6 mol/L) in the arteries. 5. NO₂Arg (3 × 10^?5 mol/L) inhibited the Sub-P (10^?12-10^?8 mol/L) induced relaxation in the canine middle cerebral artery as much as in the basilar artery. NO₂Arg (3 × 10^?5 mol/L) also inhibited Sub-P (10^?12-10^?8 mol/L) induced relaxation in the femoral artery, but the degree of the inhibition was less than that in the basilar artery. 6. These results suggest that the endothelium-derived relaxing factor (EDRF) of canine basilar artery is mainly l-Arg derived nitric oxide which may play a more important role in the basilar artery than the femoral artery.     

γ-氨基丁酸对离体犬脑血管的作用

用离体犬脑血管(基底动脉)环标本,观察γ-氨基丁酸(GABA)对几种不同激动剂所致最大收缩反应的舒张作用。苯福林(PE)10μmol·L^-1,5-羟色胺(5-HT)10μmol·L^-1以及25mmol·L^-1的KCl均可使脑血管静息张力增加,GABA50μmol·L^-1对以上几种激动剂所致的收缩反应均有舒张作用。对较高浓度的KCI(45mmol·L^-1)所致的收缩无影响,但对由冷刺激(未预热的营养液,28℃)引起的收缩反应有明显的舒张作用。     

EFFECTS OF RESERPINE ON THE CONTENT AND UPTAKE OF DOPAMINE AND NORADRENALINE IN RABBIT ARTERIES

1. Change with time of the content and uptake of dopamine (DA) and noradrenaline (NA) in the renal, superior mesenteric and femoral arteries and abdominal aorta of rabbit after reserpine administration was examined. Endogenous DA and NA were measured by high performance liquid chromatography coupled with electrochemical detector. 2. A single dose of reserpine (3 mg/kg, i.p.) maximally depleted the endogenous DA and NA contents in the four blood vessels 24 h after the administration; the ratios of reductions were 70–90% and approximately 90% of the normal levels, respectively. The DA contents in all four vessels recovered to the normal level within 4 days after reserpine. However, NA content did not recover to the normal levels within 30 days after reserpine except in the mesenteric artery. 3. The activity of dopamine β-hydroxylase (DBH) significantly increased in all four blood vessels 1 h after reserpine. Although the DBH activity returned to the normal level after 3 days in the mesenteric artery, it returned within 24 h in the other three vessels. 4. [³H]-Dopamine and [³H]-NA uptake were almost completely depressed 1 h after reserpine. The [³H]-NA uptake in four vessels recovered to the normal level 2–14 days after reserpine, and [³H]-DA uptake recovered after 30–45 days. Thus, the endogenous DA content in blood vessels was completely restored although DA uptake and NA content were still affected. 5. These results suggested that the recovery of stored DA after reserpine was faster than that of stored NA and the recovery of DA uptake after reserpine was slower than NA uptake. This indicates a possibility that a part of DA pool may be different from NA pool in adrenergic nerve terminals in the blood vessels.     

EFFECTS OF CILAZAPRIL ON THE STRUCTURE OF MESENTERIC RESISTANCE ARTERIES OF NEW ZEALAND GENETICALLY HYPERTENSIVE AND NORMOTENSIVE CONTROL RATS

1. New Zealand genetically hypertensive (GH) rats and their normotensive controls (N) rats between the ages of 10 and 16 weeks were treated with cilazapril in the diet for 6 weeks. 2. Systolic blood pressure (SBP; tail-cuff) was measured weekly and intra-arterial blood pressure (BP) was measured at the end of the treatment period. 3. The effect of cilazapril on the structure of mesenteric resistance arteries (MRA) was evaluated by both stereological and myographic techniques. 4. Cilazapril lowered SBP significantly throughout the treatment period (16 weeks; GH with cilazapril 135 ± 5 vs GH 216 ± 9 mmHg, P < 0.001; N cilazapril 91 ± 6 vs N 137 ± 3 mmHg, P < 0.001); intra-arterial BP was also significantly lowered. 5. Bodyweight (BW) of treated GH rats was significantly lower than that of untreated GH at 16 weeks (P < 0.01; t-test); however, the weight of treated N rats was not significantly affected. Ventricular mass was reduced by cilazapril in GH and N rats (GH 259 ± 10 vs 306 ± 11, P < 0.001; N 171 ± 3 vs 195 ± 4 mg/100g BW, P < 0.001). 6. Lumen volume of MRA was not significantly affected by cilazapril in either strain; media volume was reduced by 14% in both strains and the media/lumen ratio was significantly reduced. Vascular smooth muscle cell density significantly increased in cilazapril-treated GH rats.