花生四烯酸、二十碳五烯酸及二十二碳六烯酸对兔主动脉条张力的影响

外源性AA引起兔动脉条收缩,呈剂量依赖性;EPA抑制AA收缩血管亦呈浓度依赖性;DHA对AA收缩血管作用无明显影响。破坏血管内皮后AA收缩血管作用大为减弱,EPA抑制AA收缩血管作用也几乎消失。吲哚美辛能阻断AA收缩兔主动脉条的作用。兔主动脉6-keto-PGF_(1α)、TXB_2及其比值随AA浓度升高而增加,低剂量EPA对前列腺素类代谢无明显影响,较大剂量时则降低上述指标。     

双氢杨梅树皮素对兔胸主动脉条平滑肌收缩反应的影响

用兔胸主动脉条研究双氢杨梅树皮素对去甲肾上腺素(NE)、KCl和CaCl₂所致兔胸主动脉条收缩反应量效曲线的影响。双氢杨梅树皮素能显著地抑制NP、KCl和CaCl₂所致兔胸主动脉杂的收缩,量效曲线右移,最大反应降低,对高K⁺所致兔胸主动脉条收缩的抑制作用明显大于NE所致兔胸主动脉条收缩的抑制作用。双氢杨梅树皮素对NE引起的依赖内Ca²⁺释放的收缩有明显抑制作用,而对NE依赖细胞外Ca²⁺性收缩区在较高浓度时才显示抑制作用,提示双氢杨梅树皮素可能对电压依赖性钙通道(PDC)有选择性阻滞作用。     

甲基莲心碱对兔血小板聚集功能的影响

用比浊法和放射免疫分析技术研究甲基莲心碱(Nef)抗血小板聚集作用及其对TXA₂/PGI₂与cAMP/cGMP浓度的影响。结果显示,Nef在体外明显抑制ADP,胶原,AA及PAF诱导的家兔血小板聚集,IC₅₀分别为16,22,193及103μmol·L^-1;Nef明显抑制AA诱导的血小板TXA₂的生成和释放,对动脉环PGI₂的生成有促进作用;Nef剂量依赖性地升高血小板cAMP浓度,对cGMP无明显影响。结果提示Nef抗血小板聚集作用的机理与抑制TXA₂生成,增加血管PGI₂及血小板cAMP含量有关。     

阿托品对兔胸主动脉平滑肌收缩和细胞增殖的影响

用兔胸主动脉条研究Atr,Ver对CaCl₂,Atr对KCI量—效反应的影响。观察到Atr和Ver能抑制2种激动剂所致兔主动脉条的收缩,量一效曲线右移,最大反应降低,其pD₂值分别为4.4和5.8。两药也能明显抑制NE依内Ca²⁺性收缩,Atr对NE依外Ca²⁺性收缩影响较小,说明Atr主要对细胞外Ca²⁺经PDC所致的收缩有抑制作用。在兔ASMC培养中,有Ca²⁺时,Atr抑制ASMC增殖,无Ca²⁺时,Atr 20.6～185.2 μmol/L表现刺激增殖,555.7～1666.7 μmol/L则抑制MSMC增殖,说明Atr对ASMC作用也与Ca(2+)有关。     

蝙蝠葛酚性碱对血栓形成和血小板聚集的影响蝙蝠葛酚性碱对血栓形成和血小板聚集的影响

目的观察蝙蝠葛酚性碱(PAMD)对血栓形成、血小板聚集的影响并研究其作用机制。方法用动静脉短路血栓形成模型观察血栓形成；比浊法测定血小板聚集度；电镜技术观察血小板超微结构变化；放射免疫法测定TXB₂和6-酮基-PGF1α的水平；硝酸还原酶法测定兔血浆NO浓度。结果PAMD体内给药可剂量依赖性地抑制血栓形成及由ADP，AA和THR诱导的大鼠和兔的血小板的聚集；可显著抑制血小板超微结构的变化；能明显升高兔血管壁6-酮基-PGF1α产生量，对血小板释放的TXB₂无明显影响；还可提高兔血浆NO的浓度。结论PAMD具抗血栓形成和抗血小板聚集的作用，其机制与增加血管壁PGI₂含量，提高兔血浆NO的浓度有关。     

蝙蝠葛碱对血小板聚集及花生四烯酸代谢的影响

蝙蝠葛碱(Dau) 抑制AA及ADP诱导的大鼠血小板聚集,也能抑制AA,ADP及Adr诱导的人血小板聚集。这种抑制作用与Dau剂量呈依赖关系。Dau抑制大鼠洗涤血小板对[1-¹⁴C]AA经环氧酶途径的代谢,TXB₂与HHT的形成均呈剂量依赖性减少。当Dau浓度达到0.1 mmol/L时亦能抑制12-HETE的形成。Dau对AA代谢的上述影响可能是其抑制血小板聚集的机理之一。     

异莲心碱对麻醉大鼠血流动力学及平滑肌收缩反应的影响

异莲心碱2.5-10 mg·kg^-1 iv可剂量依赖性地一过性轻度降低麻醉大鼠心率, 收缩动脉压, 平均动脉压, 舒张动脉压, 左室收缩压, 左室压力最大变化速率,而对左室舒张末压无显著影响. 异莲心碱使甲氧明所致兔主动脉环和大鼠肛尾肌收缩的量 效曲线平行右移,最大反应不降低,pA₂分别为6.25和6.15,对高K⁺所致兔主动脉环收缩也有明显抑制作用. 异莲心碱还明显抑制去甲肾上腺素引起的兔主动脉环依内钙和外钙的收缩反应. 结果表明,异莲心碱对α₁受体有较为明显的阻断作用,并可抑制该受体引起的内钙释放和外钙内流,对电压依赖性钙通道也有阻滞作用. 异莲心碱的一过性轻度降压和抗心律失常作用可能与这些均有关.     

哇巴因对豚鼠主动脉环平滑肌作用及与Ca2+、去甲肾上腺素的相互关系

目的观察哇巴因（ouabain,Oua）对豚鼠血管平滑肌的作用，及其与Ca₂₊和去甲肾上腺素（NE）的相互作用关系。方法利用豚鼠离体胸主动脉环，观察药物对其张力的影响。结果无论有无内皮存在，Oua均能剂量依赖性地直接收缩血管平滑肌。在无钙溶液中，Oua不能引起血管收缩。Oua可使ＮＥ的量效曲线平行左移，E_max不变；Oua可使CaCl₂的量效曲线左移上移，E_max增大。硝苯地平和维拉帕米可使Ｏua所致的血管收缩曲线下降。结论Oua所致的血管收缩作用不依赖于血管内皮的存在，但依赖于细胞外钙，并且能被钙拮抗剂所拮抗；NE与Oua，Ca₂₊对血管平滑肌的收缩呈协同作用。     

利多卡因对离体兔胸主动脉环收缩的影响

以维拉帕米(verapamil,Ver)作对照,在离体兔胸主动脉环上对利多卡因(lidocaine,Lid)松弛血管平滑肌的机理进行了探讨。Lid对高K+去极化主动脉环收缩和Ver一样有明显的松弛作用。对去甲肾上腺素(NA)引起主动脉环收缩的试验中,Lid和Ver都能抑制细胞内Ca²⁺的释放,但不抑制外Ca²⁺内流。Lid对KCl,NA量-效曲线产生非平行右移,最大反应压低,且对KCl的抑制作用大于NA,说明Lid对PDC通道有选择性阻滞作用,而对ROC通道相对不敏感。对CaCl₂量-效曲线也产生非平行右移且最大反应压低,呈非竞争性拮抗。初步提示Lid在一定浓度下有拮抗Ca²⁺的作用,这种作用为非特异性,是松弛血管平滑肌机理之一。     

不同钾通道阻滞剂对大鼠血管平滑肌的影响

目的：研究几种不同钾通道阻滞剂对血管平滑肌的影响。方法：大鼠离体胸主动脉条张力记录法。结果：BaCl₂,4-AP,CsCl和TEA均能浓度依赖的引起大鼠离体胸主动脉条收缩, 其中BaCl₂引起血管收缩的作用明显强于其它3种化合物,EC₅₀值为90　μmol.L^-1。而E-4031、索他洛尔和格列本脲对血管张力没有影响;此外E-4031、索他洛尔和4-AP还可抑制去甲肾上腺素引起的血管收缩。结论：E-4031、索他洛尔和格列本脲在正常治疗浓度下对血管平滑肌的张力影响不大;并提示不同的钾通道阻滞剂其组织选择性存在明显差异。     

阿魏酸钠对花生四烯酸代谢的影响

利用放射薄层方法测定兔血小板花生四烯酸代谢产物TXB₂,PGE₂和PGF_2α。用放射免疫法测定兔血小板TXB₂及主动脉6-keto-PGF_1α。阿魏酸钠(SF,0.1～3.2 mmol/L),抑制¹⁴C-花生四烯酸转化为TXB₂,呈剂量效应关系,IC₅₀为0.762 mmol/L。SF在较高浓度(0.8～3.2mmol/L)时亦抑制PGE₂,PGF_2α的生成。用放免法观察到,SF对血小板TXB₂和动脉壁6-keto-PGF_1α的生成均有抑制作用,对TXB₂的作用较强。结果提示,SF可抑制兔血小板和动脉壁环氧酶活性。     

乙酰丹酚酸A对血小板花生四烯酸代谢的影响

乙酰丹酚酸Ａ对血小板花生四烯酸代谢的影响吁文贵徐理纳（中国医学科学院、中国协和医科大学药物研究所，北京１０００５０）乙酰丹酚酸Ａ（ａｃｅｔｙｌｓａｌｖｉａｎｏｌｉｃａｃｉｄＡ，ＡＳＡＡ）在体内外能明显抑制花生四烯酸（ａｒａｃｈｉｄｏｎｉｃａｃｉｄ，Ａ...     

二十碳五烯酸抗拴作用的实验研究

对二十碳五烯酸(EPA)的抗栓作用及其机制进行了研究。结果表明,EPA在体内、体外均有明显抗栓作用,并能增强纤溶活力,缩短优球蛋白溶解时间,抑制花生四烯酸和胶原诱导的大鼠血小板聚集。放射免疫测定证明,EPA能降低小鼠血浆血拴素B_2(TXB_2)含量,提高6-酮前列腺素F_(1α)与TXB_2的比值。     

Inhibitory effect of dietary administration of eicosapentaenoic acid on the contractions of guinea-pig tracheal smooth muscle induced by leukotriene C4 and D4

The changes in fatty acid composition in phospholipids of guinea-pig lung parenchymal strips and trachea induced by dietary administration of eicosapentaenoic acid (EPA) were investigated as well as the resultant changes in leukotriene (LT) C4- and D4-induced contractions of guinea-pig tracheal smooth muscle. EPA levels in both parenchymal strips and trachea were significantly increased depending on the administered dose of EPA, but on the other hand, arachidonic acid levels in those preparations were not changed. Both the contractions of guinea-pig tracheal smooth muscle induced by LTC4 and D4 were significantly reduced in the EPA-treated group compared with the control group at all 3 concentrations, 10(-9), 3 x 10(-9) and 10(-8) mol/l, in the presence of 5 x 10(-5) mol/l indometacin, a cyclooxygenase inhibitor. But this significant reduction of the contraction was not recognized between these 2 groups in the presence of 10(-5) mol/l 2-(12-hydroxydodeca-5, 10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone (AA861), a 5-lipoxygenase inhibitor, or in the combined presence of 5 x 10(-5) mol/l indometacin and 10(-5) mol/l of AA861. These results suggest that: 1. a 5-lipoxygenase pathway is partly involved in the contractions of guinea-pig tracheal smooth muscle induced by LTC4 and D4 and; 2. EPA suppresses LTC4- and D4-induced contractions of guinea-pig tracheal smooth muscle through a 5-lipoxygenase pathway.     

RENAL PROSTAGLANDIN EFFLUX INDUCED BY VASOPRESSIN, DDAVP AND ARACHIDONIC ACID: CONTRASTING PROFILE AND SITES OF RELEASE

Prostaglandin (PG) efflux into ureteral (UE) and venous effluents (VE) of rabbit isolated perfused kidneys was determined by superfusion bioassay and radioimmunoassay (RIA), in response to injections of arginine-vasopressin (AVP), the non-pressor vasopressin analogue 1-deamino-8-D-arginine vasopressin (dDAVP) and arachidonic acid (AA). dDAVP (10-1000 ng) failed to stimulate renal PG release, whereas AVP (10-100 ng) and AA (10-50 micrograms) caused a dose-dependent release of PG. AVP evoked PG release into both effluents with release into the VE greater than UE at high doses. In contrast, PG release by AA was almost exclusively into the VE. Indomethacin (2.8 X 10(-6) mol/l) abolished AVP- and AA-induced PG efflux in both effluents, and vasodepressor responses to AA. PGE2 was the predominant PG released in response to AVP in both effluents whereas AA released primarily 6-keto-PGF1 alpha. The contrasting sites and profile of released PG suggest that exogenous AA and AVP stimulate the release of PG from different regions/cell types within the kidney.     

ARACHIDONIC ACID METABOLISM IN NICOTINE-TREATED RATS AND NICOTINE-INCUBATED RABBIT AORTIC SMOOTH MUSCLE CELLS

1. The changes in plasma levels of thromboxane-B2 (TXB2) and 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) were examined in rats given 5, 25, 50 or 100 micrograms/mL nicotine in drinking water for 10 days. 2. The effect of nicotine on prostacyclin (PGI2) synthesis from endogenous arachidonic acid by cultured rabbit aortic smooth muscle cells was also studied. 3. Plasma levels of TXB2 were increased dose-dependently by treatment for 10 day with nicotine. 4. 6-Keto-PGF1 alpha values were lowered dose-dependently, both in the plasma of nicotine-treated rats and in rabbit aortic smooth muscle cells incubated with the alkaloid. 5. The results suggest that endogenous synthesis of thromboxane-A2 and PGI2, as reflected by TXB2 and 6-keto-PGF1 alpha levels, respectively, is influenced by nicotine treatment. These findings may be related to cardiovascular diseases associated with cigarette smoking, but further studies are needed.     

山莨菪碱对大鼠胸水中性白细胞花生四烯酸代谢的影响

本文研究了654-2对大鼠胸水中性白细胞代谢[1-¹⁴C]AA及内源性AA的影响。大鼠白细胞AA经5-LPO代谢途径形成的主要产物为LTB₄及5-HETE,经CO途径的主要产物为HHT及TXB₂。654-2对白细胞代谢[1-¹⁴C]AA无抑制作用,但显著减少白细胞从内源性AA形成的LTB₄,5-HETE,HHT及TXB₂。这种抑制作用与654-2呈剂量依赖关系。本实验结果表明,654-2抑制PG及LT的形成可能是影响了AA从胞膜的释放,而并非直接抑制CO及5-LPO。     

Contraction and prostaglandin biosynthesis by myometrium from non-pregnant and pregnant rabbits in response to adenosine 5'-triphosphate

In both non-pregnant and pregnant rabbit myometrial strips, adenosine 5'-triphosphate (ATP) produced contractions in a concentration-dependent manner. Furthermore, ATP (100 microM and 1 mM) produced an initial rapid twitch-like contraction followed by augmented spontaneous motility. These contractile responses of strips from pregnant rabbits to ATP were more marked than those of strips from non-pregnant rabbits. The pD2 values for the contractile response to ATP were 5.20 and 6.70 in strips from non-pregnant and pregnant rabbits, respectively. Treatment with indomethacin did not affect the initial rapid twitch-like contraction, but inhibited the augmented spontaneous motility. ATP also increased the synthesis of prostaglandins (PGs) and thromboxane B2 (TXB2) in a concentration-dependent manner in the following order: 6-keto-PGF1 alpha greater than PGE2 greater than PGF2 alpha greater than TXB2. The increase in the synthesis of cyclooxygenase products induced by ATP was more marked in strips from pregnant rabbits than in strips from non-pregnant rabbits. ATP and melittin stimulated arachidonic acid, phosphatidic acid and diacylglycerol formation in strips from both non-pregnant and pregnant rabbits. These results indicate that ATP stimulates PGs and TXB2 synthesis and phosphatidylinositol hydrolysis through an effect on P2-purinoceptors and consequently augments myometrial contractility in both non-pregnant and pregnant rabbits.     

The cyclo-oxygenase pathway in the avascular heart of the frog, Rana esculenta L

A modification of Vane's cascade is reported, allowing the superfusion bioassay of prostaglandin-like substances (PLS) in the outflow of isolated and perfused heart of the frog Rana esculenta L. Using both this technique and radioimmunoassay determination, the cyclo-oxygenase pathway in perfused frog heart has been investigated. Arachidonate (AA) (2-20 micrograms) injected into the perfusing fluid, was transformed by the heart into PLS, as shown by the response of the bioassay tissues (rat stomach strip, chick rectum, rat colon). A compound capable of relaxing rabbit mesenteric artery and a rabbit aorta contracting substance were also generated. The release was inhibited by indomethacin (1.0 X 10(-5)M). Radioimmunoassay determination of PGE2, TXB2 and 6-keto-PGF1 alpha in frog heart effluent, before and after AA injection (20 micrograms), gave the following yields (ng/ml of effluent). Basal: PGE2 = 0.45 +/- 0.15; TXB2 = 0.46 +/- 0.13; 6-keto-PGF1 alpha = 2.21 +/- 0.3. Following AA: PGE2 = 1.55 +/- 0.35; 6-keto-PGF1 alpha = 3.4 +/- 0.4; TXB2 = 1.00 +/- 0.06. Our results suggest that prostacyclin is a major product of the cyclo-oxygenase pathway in frog perfused heart. The biological significance of this finding is discussed in relation to both the absence of a coronary circulation in amphibians and to the spongy nature of frog myocardium.     

Effects of endocrine disruptors on arachidonic acid metabolism in rabbit platelets

To explore the possible actions of endocrine disruptors on the autacoid synthesis in the body, we investigated the effects of nonylphenol (NP), bisphenol A (BPA), di-n-butyl phthalate (DBP), benzyl-n-butyl phthalate (BBP), and di-2-ethylhexyl phthalate (DEHP) on the formation of 12-lipoxygenase metabolite, 12-HETE, and cyclooxygenase metabolites, TXB(2) and 12-HHT, from exogenous arachidonic acid (AA) in rabbit platelets. NP (10-50 microM) showed strong inhibition on the formation of cyclooxygenase metabolites (TXB(2), 34-95% inhibition; 12-HHT, 13-78% inhibition) and weaker inhibition on the formation of 12-HETE (0-49% inhibition). BPA, DBP, BBP, DEHP, and 17beta-estradiol (endogenous estrogen) failed to show any effect on the formation of cyclooxygenase and 12-lipoxygenase metabolites at concentrations up to 100 microM. These results suggest that NP inhibits AA metabolism in platelets and that its effects on the cyclooxygenase pathway predominate over those exerted via the 12-lipoxygenase pathway.