A METHOD FOR EXAMINING TURNOVER AND SYNTHESIS OF PALMITATE-CONTAINING BRAIN LIPIDS IN VIVO

1. A theoretical three compartment model is presented which gives the rate of incorporation of plasma palmitate into brain, Jpalm, in terms of turnover and synthesis of palmitate-containing lipids, de novo synthesis of palmitate from acetate, and recycling of palmitate within lipids. 2. Jpalm equals 4 h brain radioactivity following intravenous injection of [U-14C]-palmitate (determined with quantitative autoradiography), divided by integrated plasma specific activity of palmitate. Jpalm follows the time course of brain lipid synthesis during development of the rat, but is age-invariant in the adult. 3. At 1-7 days after 5 min of bilateral carotid occlusion in the awake gerbil, intravascular [14C]-palmitate incorporation is reduced in the CA1 pyramidal layer of the hippocampus, consistent with delayed neuronal death, but is elevated in the CA3 and CA4 pyramidal layers and dentate gyrus, suggesting synthesis of new membrane during recovery from the ischaemic insult. 4. Several weeks after unilateral destruction of the cochlea in 11 day old rats, incorporation of [14C]-palmitate from plasma into appropriate central auditory regions is reduced, corresponding to reduced cell size and altered morphology. 5. [14C]-palmitate incorporation into the left hypoglossal nucleus is increased during and following axonal regeneration (up to 23% compared with control side) following transection of the left hypoglossal nerve in Fischer-344 rats, whereas incorporation is decreased 6-7% when regeneration is prevented. Time courses of incorporation in both cases correspond to histological changes. 6. The results show that the palmitate method can be used to examine regional turnover and synthesis of brain lipids following injury, sensory deprivation, development, regeneration and ageing.     

Effect of 4-(4'-chlorobenzyloxy)benzyl nicotinate (KCD-232) on cholesterol metabolism in rats

The effects of 4-(4'-chlorobenzyloxy)benzyl nicotinate (KCD-232), a new hypolipidemic agent, on serum cholesterol level and cholesterol biosynthesis were studied in normolipidemic rats. KCD-232 dose-dependently reduced the serum cholesterol level. The in vivo incorporation of [14C]-acetate and 3H from [3H]water into liver digitonin-precipitable sterols was inhibited by oral administration of KCD-232, while that of [14C]mevalonic acid into the sterols was not inhibited. Hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity was suppressed significantly by the oral administration of the drug. A KCD-232 metabolite, 4-(4'-chlorobenzyloxy)benzoic acid (MII), strongly inhibited [14C]acetate incorporation and weakly inhibited [14C]mevalonic acid incorporation into the sterols in liver slices. MII also significantly inhibited the sterol synthetic rate measured with [3H]water and the HMG-CoA reductase activity in dispersed hepatocytes. MII and its CoA thioester (MII-CoA) inhibited the incorporation of [14C]acetate, [14C]acetyl-CoA and [14C]HMG-CoA into nonsaponifiable lipids in a cell-free enzyme system from rat liver. MII-CoA further showed a weak inhibition of [14C]-mevalonic acid incorporation into nonsaponifiable lipids in the system, while MII showed no effect on mevalonic acid incorporation. These results indicate that KCD-232 possesses a major inhibitory site for sterol synthesis on HMG-CoA reductase due to both MII and MII-CoA, and a possible second site of action beyond mevalonic acid due to MII-CoA. The latter inhibitory site, however, is considered to play a minor role in the inhibition of sterol synthesis in vivo.     

Changes in extracellular calcium within the physiological range influence receptor-mediated inositol phosphate responses in brain and tracheal smooth muscle slices

Summary The effect of changes in extracellular calcium concentration ([Ca²⁺]_e) on the incorporation of myo-[2-³H]-inositol into phosphoinositides and agonist-stimulated ³H-inositol phosphates (³H-InsPs) was examined in rat cerebral cortex and bovine tracheal smooth muscle slices. In brain slices, reduction in [Ca²⁺]_e from 2.4 to 1.2 mmol/l resulted in an approximate doubling of the carbachol and noradrenaline-stimulated ³H-InsP response with no effect on the EC₅₀ values. An identical effect of varying [Ca²⁺]_e was observed for carbachol-stimulated ³H-InsP formation in tracheal smooth muscle with a further increase in ³H-InsPs evident at [Ca²⁺]_e 0.6 mmol/l. In this tissue the effect of changes in [Ca ²⁺]_e on the incorporation of myo-[2-³H]-inositol into the total phosphoinositide pool directly paralleled the changes in ³H-InsPs except in conditions of no added calcium when ³H-InsP responses were markedly impaired. Additional studies in brain slices using buffer where the added calcium varied between 0 and 2.4 mmol/l, showed that both the carbachol stimulated formation of separate inositol phosphates during short incubation periods and incorporation of myo-[2-³H]-inositol into PtdInsP and PtdInsP₂ under basal conditions was maximal at [Ca²⁺]_e 0.3 mmol/l. Omitting Ca²⁺]_e from the buffer resulted in maximal labelling of PtdIns but a decrease in PtdInsP and PtdInsP₂ labelling (compared with the level at [Ca²⁺]_e 0.3 mmol/l) and a markedly impaired inositol polyphosphate response. Alterations in [Ca²⁺]_e following ³H-inositol labelling but immediately prior to carbachol stimulation did not influence ³H-inositol polyphosphate responses. It is therefore clear that even relatively small changes in [Ca²⁺]_e markedly influence agonist-stimulated ³H-InsP responses in brain and tracheal smooth muscle slices and that these reflect changes in the labelling of substrate inositol lipids. These findings have important practical implications for studies examining ³H-InsP responses in central and peripheral tissues and the differential effect of very low [Ca²⁺]_e on PtdIns and PtdlnsP/PtdInsP₂ labelling may explain in part the severe decrease in ³H-InsPs seen under these conditions despite apparent maximal total phosphoinositide labelling. Send offprint requests to S. R. Nahorski at the above address     

绿茶儿茶酚抑制血管收缩及动脉平滑肌细胞增生(英文)

目的:本文研究从绿茶分离提纯儿茶酚衍生物的血管舒张和抗平滑肌细胞增生的作用.方法:测定分离的大白鼠动脉及肠系膜动脉的收缩力以及动脉平滑肌增生能力.结果:儿茶酚混合物以及其中两个衍生物(表儿茶酚和没食子表食子儿茶酚)浓度依赖性地舒张去甲肾上腺素收缩的动脉以及抑制血管平滑肌细胞增生.结论:绿茶分离提纯儿茶酚混合物及其中两个衍生物具有血管舒张的功能.而它们抗血管平滑肌细胞增生的作用更为显著.没食子表食子儿茶酚是绿茶儿茶酚混合物的主要成份,它的药理作用明显强过表儿茶酚.     

Influence of Silybin-dihemisuccinate on fatty acid synthesis in rat liver (author's transl)]

1. The influence of silybin-dihemisuccinate, a derivative of the flavonolignane silybin from silybum marianum L. Gaertn., on fatty acid biosynthesis of rat liver was studied measuring the radioactivity incorporation of [1-14C]-acetate and 3H2O in fatty acids of the postmitochondrial supernatant of liver homogenates and in fatty acids of liver slices as well as the activities of enzymes involved in do novo synthesis of fatty acids. 2. In the postmitochondrial supernatant of liver homogenates or in liver slices, prepared 30 or 60 min after i.v. injection of 150.6 mg/kg silybin-dihemisuccinate, radioactivity incorporation of 14C-acetate or 3H2O in fatty acids was lowered by about 25%. Adding silybin-dihemisuccinate to incubation mixture in vitro in the concentration of 0.45--0.6 mmol/l silybin the radioactivity incorporation was linearly diminished with increased concentration of silybin. 3. After in vitro addition of varying concentrations of silybin to incubation mixtures in the presence of 0.1 mmol/l silybin activities of acetyl-CoA-carboxylase, fatty-acid-synthetase and ATP-citrate-lyase were diminished by about 50%, while activity of NADP-malate-dehydrogenase was lowered by 20% in the presence of 1 mmol/l silybin. 4. Our results suggest that silybin caused an unspecific and, under in vivo conditions, transitory inhibition of fatty acid synthesis in rat liver.     

Cardenolide and Neutral Lipid Biosynthesis from Malonate in Digitalis lanata

DIGITALIS LANATA plants were grown on water culture in a controlled environment and in the young, growing leaves free sterols (0.335 micromol/g FW), triacylglycerols (0.97 micromol/g FW) and cardenolides (1.82 micromol/g FW) were the major apolar and polar lipids. The cardenolide-containing fraction from these tissues was separated into 26 cardenolides by HPLC. The 5 major components (accounting for 60 % of the occurring glycosides) lanatosides A and C, acetyldigoxin, acetyldigitoxin, and glucoevatromonoside were identified by FABMS. Incorporation experiments with [2- (14)C]-acetate, [2- (14)C]-malonate, [2- (14)C]-mevalonate, and [U- (14)C]-sucrose (absorbed by excised, young, growing leaves) showed the labelling of all the occurring cardenolides after a 3 day incorporation period (as judged by HPLC). Comparing the simultaneous synthesis of labelled sterols and triacylglycerols, malonate could be considered as the most effective precursor in cardenolide synthesis, reaching an incorporation value of 4.1 % in a 4 day incorporation period. A time-course experiment revealed a temporary accumulation of (14)C in glucoevatromonoside, which may play a role as an intermediate in cardenolide production of DIGITALIS LANATA.     

Influence of muzolimine on arterial wall elastin

Muzolimine, 3-amino-1-(3,4-dichloro-alpha-methylbenzyl)-2- pyrazolin -5-one, an antihypertensive and diuretic drug, accumulates in the arterial tissue of rats and dogs after oral administration. Two weeks after the administration of 3 mg [14C]muzolimine, the aorta of rats contained 60-300 times more 14C-radioactivity/weight unit than the skin or tail tendon. The 14C-radioactivity was exclusively bound to the isolated aortic elastin and corresponded to 0.04% of the applied muzolimine dose. Up to ca 250 ng bound muzolimine/mg elastin was found in the aorta of dogs treated with non-labelled muzolimine for 52 weeks. The elastin-bound [14C]muzolimine was not extractable by organic solvents or by weak acids or bases but was released in a soluble form by pancreatic elastase and extracted from the elastase digest by dichloromethane. In the dichloromethane extract muzolimine was detected by HPLC and HPTLC, and was identified by mass spectrometry. Muzolimine pretreatment of rats for 2 months did not influence the elastin content of arterial tissue or [3H]glycine incorporation into aortic elastin under organ culture conditions, but after labelling the elastin with [4,5-3H]lysine, the [3H]desmosine and [3H]-isodesmosine isolated from the elastin of muzolimine-pretreated rats and incorporated under organ culture conditions was lower than that of control animals. In addition, aortic elastin of rats pretreated for 2 months with 800 ppm muzolimine in the diet was more resistant to elastase degradation. This effect might give some implications for muzolimine in the therapy of cardiovascular disorders with impaired arterial elastin metabolism.     

The influence of 2-ethyl-3-(4-hydroxy-benzoyl)- benzofuran on the contraction of pial arterial muscles (author's transl)]

By means of perivascular perfusion of thin sections of pial arteries with differently composed cerebrospinal fluid (CSF) the vessel diameters can be influenced. In cats, anesthetized with pentobarbital, addition of serotonin, norepinephrine or calcium to an artificial CSF which was infused through micropipettes into the perivascular space of the pial arteries, caused constrictions of the arteries contacting the modified CSF. Hyperventilation or perivascular perfusion of alkaline CSF also caused reduction of the pial arterial diameters. 2-Ethyl-3-(-hydroxy-benzoyl)-benzofuran (benzarone) inhibited or abolished the constrictions elicited by the above mentioned stimuli. The effect was dose-dependent. High doses of benzarone caused pial arterial dilations: The inhibition of the calcium induced constriction especially, seems worth mentioning since this ion plays a central role in the contraction mechanisms of the vascular smooth muscle cells.     

Carvedilol inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. Inhibition of proliferation of pulmonary artery smooth muscle cells (PASMCs) may be an effective treatment of patients with idiopathic pulmonary arterial hypertension. Recent studies have shown that carvedilol, an alpha- and beta-blocker with antioxidant and calcium channel blocking properties, inhibits the proliferation of cultured normal human pulmonary artery smooth muscle cells. In this study, we tested the hypothesis that carvedilol has antiproliferative effects on pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Pulmonary artery smooth muscle cells from six idiopathic pulmonary arterial hypertension patients who had undergone lung transplantation were cultured. To determine cell proliferation, H-thymidine incorporation was measured. Platelet-derived growth factor-induced proliferation of IPAH-PASMCs was significantly greater than that of normal control pulmonary artery smooth muscle cells. Carvedilol (0.1 microM to 10 microM) inhibited the proliferation of idiopathic pulmonary arterial hypertension-pulmonary artery smooth muscle cells in a concentration-dependent manner. Prazosin (an alpha-blocker) and N-acetyl L cysteine (an antioxidant agent) (0.1 microM to 10 microM) did not inhibit their proliferation, but the high concentration of propranolol (a beta-blocker) and nifedipine (a calcium channel blocker) (10 microM) inhibited the proliferation. The combination of propranolol and nifedipine inhibited the proliferation but only at a high concentration (10 microM) combination. Cell cycle analysis revealed that carvedilol (10 microM) significantly decreased the number of cells in S and G2/M phases. These results indicate that carvedilol inhibits the exaggerated proliferation of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension partially via its beta-blocking [corrected] and calcium channel blocking effects in vitro.     

Effects of dl-propranolol on the synthesis of glycerolipids by rabbit iris muscle

Propranolol (0.03?0.3 mM), an amphiphilic cationic drug which is used therapeutically as a β-blocker, was found to alter significantly the incorporation of [¹⁴C]glucose, [¹⁴C]glycerol, [¹⁴C]acetate, ³²Pi, [³H]cytidine, [³H]inositol, [¹⁴C]choline, [¹⁴C]ethanolamine and [¹⁴C]serine into phospholipids of the iris muscle. Furthermore, it was found to exert a stimulatory effect on the [¹⁴C]serine incorporation into phosphatidylserine of the muscle and microsomes. In contrast, sotalol, another β-blocker-but lacking the hydrophobicity of propranolol-exerted no effect on lipid metabolism. Whereas norepinephrine stimulated only the turnover of the phosphate moiety of phosphatidic acid and phosphatidylinositol, in general propranolol caused the following changes: (a) it stimulated by 2- to 6-fold the labelling of phosphatidic acid and phosphatidylinositol from [¹⁴C]glucose, [¹⁴C]glycerol, [¹⁴C]acetate, ³²Pi and [³H]inositol, (b) it increased by 5- and 38-fold the incorporation of ³²Pi and [³H]cytidine, respectively into CDP-diglyceride, (c) it inhibited appreciably the incorporation of [¹⁴C]glucose, [¹⁴C]glycerol, [¹⁴C]acetate and ³²Pi into phosphatidylcholine and phosphatidylethanoalmine. However, while it inhibited significantly the [¹⁴C]choline incorporation into the former, it stimulated by 60 per cent the ethanolamine incorporation into the latter phospholipid. These results indicate that propranolol probably redirects phospholipid synthesis de novo, by inhibiting phosphatidate phosphohydrolase, such that the increase obtained in the biosynthesis of phosphatidylinositol is accompanied by a corresponding decrease in the synthesis of phosphatidylcholine and phosphatidylethanolamine.Propranolol also caused a 250 per cent increase in the [¹⁴C]serine incorporation into phosphatidylserine of the iris muscle and 28 per cent increase in that of microsomes. The drug appears to stimulate the Ca²⁺ -uptake by muscle and microsomes, which in turn could act to stimulate the Ca²⁺-catalyzed base-exchange reaction.In addition the metabolic pathways involved in the biosynthesis of the major phospholipids of the iris, a smooth muscle, are reported for the first time. These pathways were found to be essentially similar to those reported for other tissues.     

Timing of Diosgenin Appearance in Suspension Cultures of Dioscorea deltoidea

Cycloheximide and compactin were added to cell suspension cultures of DIOSCOREA DELTOIDEA. Cycloheximide inhibited growth and diosgenin biosynthesis completely at 40 mg/l when added during the growth phase. Compactin partially inhibited growth and diosgenin production at 100 microg/l when added during the growth phase. [1- (14)C]-Acetate incorporation into diosgenin was about 20-fold higher when added during the early stages of growth as compared to addition in the stationary phase. Incorporation of [1- (14)C]-acetate into diosgenin was inhibited by compactin only during the early stages of growth. These results indicate the formation of an accumulating intermediary metabolite during the early stages of growth which is transformed into diosgenin when D. DELTOIDEA cells are in the stationary phase.     

Alteration of glycosaminoglycans induced by cadmium in cultured vascular smooth muscle cells

Alteration of glycosaminoglycans (GAGs) in cultured bovine aortic smooth muscle cells after exposure to cadmium was investigated. It was revealed that cadmium increased the accumulation of GAGs metabolically labeled with [³H]glucosamine but decreased that with [³⁵S]sulfate in the cell fraction, the cell surface fraction and the medium fraction. This suggested that cadmium stimulated the biosynthesis of GAGs but inhibited their sulfation in the cells. A similar alteration was observed in cadmium-treated human aortic smooth muscle cell layer. Of tested cations including cadmium, bismuth, cobalt, copper, lead, manganese, nickel and zinc, only cadmium stimulated [³H]glucosamine incorporation, with a strong inhibition of the [³⁵S]sulfate incorporation in the bovine cells. Characterization of bovine smooth muscle GAGs showed that the cadmium-induced increase in the [³H]glucosamine incorporation was mainly observed in heparan sulfate; the inhibition of the [³⁵S]sulfate incorporation occurred non-selectively. Cadmium accumulated in bovine vascular smooth muscle cells in a dose-dependent manner with an increase in the leakage of lactate dehydrogenase into the medium. The present data suggest that vascular smooth muscle cells respond to the cytotoxicity of cadmium and promote the GAG synthesis with a reduction of their sulfation. It is postulated that this response may be a defensive one to the damage of the vascular tissue caused by cadmium but would be a component of the metal-induced atherosclerosis. Received: 19 January 1994/Accepted: 5 May 1994     

KATP通道开放剂吡那地尔对兔肺动脉平滑肌细胞增殖的影响

目的 :研究吡那地尔 (pinacidil,Pin)对内皮素 1(ET 1)诱导培养的兔肺动脉平滑肌细胞 (PASMC)增殖的影响。方法 :内皮素 1刺激培养兔PASMC增殖模型 ;以氚 胸腺嘧啶核苷 ([3 H] TdR)掺入法观察细胞增殖及脱氧核糖核苷酸 (DNA)合成 ;流式细胞仪技术检测兔PASMC细胞周期。结果 :吡那地尔可剂量依赖性的抑制内皮素 1所致的 [3 H] TdR掺入量增多 ,阻止兔PASMC由静止期 (G0 G1期 )进入DNA合成期 (S期 )和有丝分裂期 (G2 M期 )。ATP敏感性钾通道 (KATP)阻断剂格列本脲可拮抗吡那地尔对 [3 H] TdR掺入的抑制作用。结论 :吡那地尔可能通过激活KATP通道抑制内皮素 1诱导兔肺动脉平滑肌细胞的增殖 ,可望用于治疗肺动脉高压时所致的肺动脉重构。     

埃他卡林对兔肺动脉平滑肌内皮细胞钙浓度的影响

目的观察埃他卡林(IPT)对内皮素1(ET-1)诱导培养的兔肺动脉平滑肌细胞(PASMC)增殖的影响,并探讨其作用机制。方法应用细胞培养、氚-胸腺嘧啶核苷([3H]-TdR)参入实验、Fluo-3和激光扫描共聚焦显微镜技术评价IPT对ET-1诱导的兔PASMC增殖及PASMC[Ca2+]i调节的作用。结果ET-1(10-7mol.L-1)使PASMC[3H]-TdR参入量增加146.8%,与对照组比较,差异有显著性(P<0.01);在相同条件下,加入ET-1的同时,分别向培养基中加入IPT10-7、10-6、10-5mol.L-1,细胞[3H]-TdR参入量分别下降(19.8±4.6)%、(41.2±9.5)%、(54.7±10.1)%,与ET-1组比较差异有显著性(P<0.01);对照组PASMC[Ca2+]i荧光强度和荧光光密度值较低;ET-1组中[Ca2+]i荧光光密度值明显增高,从73.7±10.1增加到143.8±28.2,两者比较差异有显著性(P<0.01);而IPT组细胞内荧光光密度值明显降低,仅从74.30±10.2增加到86.03±9.82,与ET-1组比较差异有显著性(P<0.01)。结论IPT可明显抑制ET-1诱导的兔PASMC增殖、DNA合成;减少钙通道的开放时间,抑制细胞内Ca2+浓度增加。     

Suppression of myocardial protein degradation by the protease inhibitor bis[ethyl(2R,3R)-3-[(S)-methyl-1-[4-(2,3,4-tri-methoxy-phenyl-methyl) piperazine-1-ylcarbonyl]butyl-carbonyl]oxiran-2-carboxylat e]sulfate under hypoxia

The synthetic protease inhibitor bis[ethyl(2R,3R)-3-[(S)-methyl-1-[4-(2,3,4-tri-methoxyphenyl-methyl) piperazine-1-ylcarbonyl]butyl-carbonyl]oxiran-2-carboxylate] sulfate (NCO-700) suppressed both activities of calcium-activated neutral protease and cathepsin B isolated from cardiac muscle, showing 50% inhibition at 46 and 0.8 mumol/l, respectively. A kinetics study using 14C-labelled NCO-700 suggested its incorporation into cultured myocardial cells, demonstrating the half-maximal saturation time at 17 min. Under both aerobic and hypoxic conditions, the reagent inhibited the peptide release from cultured myocardial cells dose-dependently. The amino acid release from heart slices of adult rabbit was also blocked by the drug under hypoxic and glucose-depleted condition. These data and the myocardial infarction size reducing action of NCO-700 might support the view that NCO-700 sensitive protease(s) - possibly, calcium-activated neutral protease and/or cathepsin B - is (are) working to induce an irreversible proteolysis in the process of myocardial cell degradation.     

13C-labelling of xanthohumol in hop cones (Humulus lupulus)

Biolabelling conditions in hop cones of xanthohumol (Xn) were studied by feeding [U-13C]glucose, [1-13C]glucose, [ring-13C6]phenylalanine, [2-13C]sodium acetate or [2-13C]malonic acid as biosynthetic precursors to hop sprouts. Quantitative 13C-NMR spectroscopic analysis of the resulting labelled Xn showed different labelling patterns and ratios depending on precursor and feeding concentrations. The highest incorporation rate was achieved with [U-13C]glucose (9.41 +/- 1.22 %). With [ring-13C6]phenylalanine only ring B was labelled (3.51 +/- 0.08 % enrichment). [2-13C]sodium acetate and [2-13C]malonic acid allowed labelling of the A-ring (1.82 +/- 0.02 % and 1.74 +/- 0.03 % enrichment). The specific labelling pattern of the prenyl side chain with [1-13C]glucose (2.36 +/- 0.27 % enrichment) confirmed the biosynthetic origin to be MEP pathway-derived. On the basis of these results radiolabelling of Xn will be performed for in vivo bioavailability studies.     

The effect of silybin dihemisuccinate on cholesterol biosynthesis in rat liver homogenates (author's transl)

The effect of silybin dihemisuccinate on the hepatic biosynthesis of cholesterol was studied by measuring the incorporation of [1-14C]-acetate and [2-14C]-mevalonate in the postmitochondrial supernatant of liver homogenates. 2. Under absolute in vitro conditions, silybin dihemisuccinate inhibits the biosynthesis of cholesterol in dependence on its concentration. With [1-14C]-acetate or [2-14C]-mevalonate the concentrations of silybin for 50% inhibition are 0.37 mM or 0.40 mM, resp. 3. 30 min after i.v. injection of 150.6 mg silybin dihemisuccinate/kg with both precursors the biosynthesis of cholesterol studied in vitro is diminished in comparison to controls. 60 min or 24 h after i.v. injection of silybin no effects on in vitro biosynthesis of cholesterol can be observed.     

脂质体携载C型利钠利尿肽对血管效应的影响

目的　观察脂质体携载Ｃ 型利钠利尿肽（ＣＮＰ） 对大鼠主动脉血管舒张、平均动脉血压和内皮素（ＥＴ） 刺激主动脉平滑肌细胞增殖的影响。方法　主动脉环灌流测定血管张力;平滑肌细胞培养;［３Ｈ］ ＴｄＲ参入测定ＤＮＡ合成;反相蒸发法制备脂质体。结果　脂质体携载ＣＮＰ的舒张主动脉和降低平均动脉压作用显著强于单用ＣＮＰ。ＥＴ刺激平滑肌细胞增殖,使ＶＳＭＣ［３Ｈ］ ＴｄＲ 参入量增加１－８ 倍。１０ －８ 、１０－ ７ 、１０－ ６ ｍｏｌ·Ｌ－１ ＣＮＰ可使ＥＴ 刺激［３Ｈ］ ＴｄＲ参入量分别下降２％ （ Ｐ＞ ０－０５）, ２１ ％ （ Ｐ＜ ０－０５） 和５５％ （ Ｐ＜０－０１） ,而同样浓度的脂质体携载ＣＮＰ 使ＥＴ 刺激ＶＳＭＣ［３Ｈ］ ＴｄＲ参入量分别下降５６％ （ Ｐ＜ ０－０１）,５９％ （ Ｐ＜０－０１） 和６６ ％ （ Ｐ＜ ０－０１）, 其作用强于ＣＮＰ。脂质体和ＣＮＰ对［３Ｈ］ ＴｄＲ 参入量与对照组相比差异无显著性。结论　脂质体携载ＣＮＰ的舒张血管、降低平均动脉压和抑制ＥＴ 刺激平滑肌细胞增殖作用强于ＣＮＰ     

Bradykinin-stimulated differential incorporation of arachidonic acid into lipids of kidney cortex and medulla

We investigated bradykinin-induced changes in the turnover of arachidonate in renal lipids of the perfused rabbit kidney. Upon hormone stimulation, this cellular system undergoes only transient dynamic changes in arachidonic acid metabolism; no loss of bradykinin effect on arachidonate release and prostaglandin generation is shown upon repeated hormone administrations during 8-9 hr of perfusion. Ureter-obstructed rabbit kidneys were perfused for 5-6 hr and then saline or bradykinin in saline was administered, followed after 10 sec by pulse labelling with [14C]arachidonate. The pattern of distribution of [14C]arachidonate in lipid fractions of the cortex showed that bradykinin caused a 2 to 2.5-fold increase in the relative incorporation of arachidonic acid into phosphatidylinositol (PI), phosphatidic acid (PA), diglyceride (DG) and triglyceride (TG) fractions and a concomitant decrease in its incorporation into phosphatidylcholine (PC) and phosphatidylethanolamine (PE). In contrast, in the medulla hormone administration caused a marked increase of arachidonate incorporation into PI and PC, and a decrease in incorporation into PE, PA, DG and TG. This differential arachidonate labelling of cortical vs medullary lipids following bradykinin stimulation suggests that the hormone activates different lipolytic processes in cortex and medulla, and promotes hydrolysis of arachidonic acid from different phospholipid pools.