体外冲击波对兔输尿管形态及组织学影响的研究

目的 :探讨冲击波 (SW )对输尿管形态的影响。方法 :将 4 2只成年兔随机分为 7组 ,每组 6只。第 1组为正常对照组 ;第 2～ 6组为液电式SW组 ;第 7组为电磁式SW组。各组接受冲击并在冲击后不同时间取材。全部标本行常规病理检查并予评分。结果 :第 2～ 5组和第 7组 ,肉眼可见焦点周围组织有出血、水肿等改变 ,输尿管直径较冲击前显著增加 (P <0 .0 1 )。光镜下可见平滑肌细胞变性及管腔狭窄 ,病理量化评分显著高于正常组 (P <0 .0 5 ) ;电镜下则有肌细胞线粒体破坏等改变。第 6组形态改变不明显 ,病理评分和正常组的区别无显著性意义。结论 :临床剂量的冲击波能导致输尿管多种病理变化。冲击后第 5天 ,输尿管形态已基本恢复正常。由液电式和电磁式冲击波所致的输尿管急性损伤程度无明显的区别     

微囊胎垂体下丘脑黑质细胞移植实验研究

微囊包膜的股垂体下丘脑黑质细胞移植于去垂体兔腹腔中，术后观察移植兔12周。结果：移植后兔血清中GH与PRL浓度可平稳在一定水平，T4浓度自第2周起开始上升并逐渐接近正常水平，兔体重于第3周起开始增加，各靶器官在12周后无明显萎缩。提示本微囊可在促垂体区（HTA）以外移植而重建正常垂体功能达12周以上。     

消炎痛对hCG诱发家兔排卵抑制的形态学研究

应用非甾体抗炎药消炎痛(20mg/kg)抑制hCG 诱发的家兔排卵,注射后的6、9、12、72小时剖腹观察排卵数,并取材进行透射电镜观察和酶组织化学观察。甾体激素合成酶类的组织化学和颗粒细胞内某些细胞器的电镜立体定量学测定结果表明:消炎痛抑制了排卵,却不影响颗粒细胞向黄体细胞的转变。透射电镜观察表明:在排卵前,实验组和对照组最明显的不同是:实验组的外膜和白膜很少见到胶原溶解现象,且表面上皮细胞内含的致密小体不释放其内容物。结果提示:消炎痛主要作用于排卵前卵泡顶部的成纤维细胞和表面上皮细胞,这可能与其抑制了某些与排卵有关的酶的释放有关。     

Only activated but not non-activated presynaptic α2-autoreceptors interfere with neighbouring presynaptic receptor mechanisms

Summary Experiments were carried out in rabbit cerebrocortical slices in order to find out whether the attenuation by presynaptic ₂-autoreceptors of effects mediated by presynaptic opioid - and adenosine A₁-receptors requires activation of the ₂-receptors. The slices were preincubated with ³H-noradrenaline and then superfused with medium containing desipramine 1 mol/l. They were stimulated electrically either with single pulses or with trains of 32 pulses at 1 Hz.The overflow of tritium elicited by a single pulse amounted to 0.21% of the tritium content of the tissue. It was Ca²⁺-dependent and tetrodotoxin-sensitive and not changed by rauwolscine 1 mol/l or yohimbine 0.3 mol/l. Ethylketocyclazocine (EK; 0.1–10 nmol/l) and R-(–)-N⁶-phenylisopropyladenosine (PIA; 1–1,000 nmol/1) potently inhibited the overflow evoked by a single pulse, and their effects were not changed by yohimbine. — The overflow of tritium elicited by trains of 32 pulses at 1 Hz amounted to 0.92% of the tritium content of the tissue and was increased approximately fourfold by yohimbine 0.3 mol/l. EK and PIA were less potent inhibitors than in the one pulse experiments. Yohimbine greatly enhanced the effects of EK and PIA. The enhancement was even more pronounced when the Ca²⁺ concentration in the medium was reduced in order to obtain a control tritium overflow similar to that evoked by 32 pulses in the absence of yohimbine.The results demonstrate that there is no ₂-adrenergic autoinhibition when noradrenaline release is elicited by a single pulse. Under these conditions, the non-activated presynaptic ₂-adrenoceptor does not interfere with presynaptic opioid - and adenosine A₁-receptor mechanisms. It is only when the autoreceptor is activated by released noradrenaline that it attenuates neighbouring presynaptic receptor mechanisms, and this attenuation is removed by ₂-adrenoceptor antagonists.Send offprint requests to N. Limberger at the above address     

Phorbol ester does not mimic,but antagonizes the alpha-adrenoceptor-mediated positive inotropic effect in the rabbit papillary muscle

Summary The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) was used to examine the hypothesis that phosphoinositide turnover is involved in the regulation of myocardial contractility mediated by stimulation of alpha-adrenoceptors in the mammalian cardiac muscle. Exposure of the isolated rabbit papillary muscle electrically driven at a rate of 1 Hz at a temperature of 37°C to TPA in concentrations of 10–1000 nmol/l for 30 min did not affect the basal force of contraction. The concentration-response curve for the positive inotropic effect of (–)-phenylephrine mediated by stimulation of alpha-adrenoceptors in the presence of (±)-bupranolol (100 nmol/1) was shifted to the right and downward by TPA in concentrations of 30–1000 nmol/l, while the effect of (–)-phenylephrine mediated by stimulation of beta-adrenoceptors in the presence of prazosin (100 nmol/l) was not decreased, but slightly enhanced by exposure of the muscle to relatively low concentrations of TPA (10–100 nmol/l). Incubation of the membrane fraction isolated from the rabbit ventricular muscle with TPA in vitro under the same condition as employed in the physiological experiments decreased the specific binding of [³H]prazosin but not that of [³H]CGP-12177, while the non-tumor promoting phorbol ester, PDD, was ineffective. These results indicate that activation of protein kinase C by TPA does not mimic the positive inotropic effect of catecholamines mediated by activation of myocardial alpha-adrenoceptors. on the other hand, the specific interaction of alpha-adrenoceptor-mediated processes with TPA in the rabbit papillary muscle is in line with the view that the facilitation of phosphoinositide turnover and subsequent activation of protein kinase C may play a certain role in the coupling of alpha-adrenoceptor occupation by agonists to the process leading to the positive inotropic action. Send offprint requests to M. Endoh     

Involvement of Ca+ mobilization in the amplifying effect of serotonin on responses of rabbit isolated ear artery to exogenous noradrenaline

Summary The present study examined the involvement of Ca⁺ mobilization in the amplifying effect of serotonin on steady-state responses of rabbit isolated perfused ear artery to exogenous noradrenaline (NA; 0.001–3 ol/l). In contrast to its marked amplifying effect on responses to NA, serotonin in the subconstrictor concentration of 100 nmol/l had no effect on responses to KCl. The Ca⁺-entry blocking drug diltiazem (10 gmol/1) decreased responses to NA; in addition, the amplifying effect of serotonin on responses to NA was reduced by diltiazem. Lowering the concentration of Ca⁺ in the Krebs-Henseleit perfusion solution from 2.5 to 0.25 mmol/l also reduced both responses to NA and the amplifying effect of serotonin. Using the method of Manzini et al. (1982), separate intra- and extracellular Ca⁺-dependent responses to NA were obtained. Serotonin had no effect on intracellular Ca⁺-dependent responses to NA but enhanced extracellular Ca²⁺-dependent NA responses. These results suggest that the amplifying effect of serotonin on responses of rabbit ear artery to exogenous NA involves a selective enhancement of the component of the NA response which is dependent on extracellular Ca⁺; serotonin may increase NA-evoked entry of Ca²⁺ into the vascular smooth muscle cells through receptor-operated Ca⁺ channels. Send offprint requests to A. G. Meehan at the above address     

ACTH increases noradrenaline release in the rabbit heart

Summary The effects of ACTH on the release of noradrenaline and the increase of heart rate produced by sympathetic nerve stimulation (1 Hz) were studied in isolated perfused rabbit hearts. ACTH-(1–24) 0.1–100 nmol/l increased the stimulation-evoked overflow of noradrenaline concentration-dependently, reversibly and up to two-fold. The basal outflow of noradrenaline, the basal heart rate and the stimulation-evoked increase in heart rate were not changed. Human ACTH-(1–39) also increased the evoked overflow of noradrenaline. The effect of ACTH-(1–24) 0.3 nmol/l persisted after blockade of -adrenoceptors with propranolol and blockade of neuronal catecholamine uptake by cocaine. ACTH-(1–24) 3 nmol/l did not change the removal of noradrenaline from the perfusion fluid, when hearts were perfused with medium containing 59 nmol/l noradrenaline. The results show that ACTH increases the action potential-evoked release of noradrenaline from cardiac postganglionic sympathetic neurones, probably by activating specific presynaptic ACTH receptors. The high potency of ACTH suggests that these presynaptic receptors may be activated in vivo by circulating ACTH under certain pathophysiological conditions.Send offprint requests to B. Szabo at the above address     

Phentolamine blocks presynaptic serotonin autoreceptors in rabbit and rat brain cortex

Summary Possible antagonist effects of phentolamine at presynaptic serotonin autoreceptors were studied in slices of the occipito-parietal cortices of the rabbit and the rat. The slices were preincubated with ³H-serotonin and then superfused and stimulated electrically with single pulses or pulse trains. Nitroquipazine 1 mol/l, a compound that inhibits the high affinity neuronal uptake of serotonin, was present in the superfusion medium in all one pulse-experiments as well as in experiments in which the effect of unlabelled serotonin was examined.In rabbit cortical slices, unlabelled serotonin reduced the single pulse-evoked overflow of tritium. Its concentrationresponse curve was not changed by the selective ₂-adrenoceptor antagonist idazoxan 1 mol/l but was shifted to the right by phentolamine 1 and 10 mol/l. Phentolamine 10 mol/l also shifted to the right the concentration-inhibition curve of the selective 5-HT₁-receptor agonist 5-carboxamidotryptamine. When the slices were stimulated by trains of 30 pulses at 3 Hz, phentolamine 1 and 10 mol/l but not 0.1 mol/l increased the evoked overflow of tritium, the maximal increase amounting to 178%; its effect was enhanced in the presence of nitroquipazine 1 mol/l plus idazoxan 10 mol/l (a drug combination that, when given alone, slightly increased the evoked overflow of tritium). The serotonin receptor antagonist metitepin at concentrations of 0.01–1 mol/l also increased the overflow of tritium elicited by 30 pulses/3 Hz, the maximal increase amounting to 280%; its effect was potentiated in the presence of nitroquipazine 1 mol/l plus idazoxan 10 mol/l but was abolished or almost abolished in the presence of nitroquipazine 1 mol/l plus phentolamine 10 mol/l (a drug combination that, given alone, greatly increased the evoked overflow of tritium). When slices were stimulated by trains of 360 pulses at 3 Hz, there was no apparent antagonism of phentolamine 10 mol/l against the inhibitory effect of unlabelled serotonin. In rat brain cortex slices, unlabelled serotonin reduced the overflow of tritium elicited by 4 pulses delivered at 100 Hz. Again, phentolamine 10 mol/l shifted the concentration-response curve to the right.It is concluded that phentolamine blocks presynaptic serotonin autoreceptors in rabbit and rat brain cortex with pA₂ values of 6.44 and 5.95, respectively. Previous failures to detect the antagonistic effect against exogenous agonists were probably due to stimulation conditions that led to marked endogenous autoinhibition of serotonin release. At least the major part of the increase by phentolamine of the release of serotonin is due to autoreceptor blockade rather than blockade of the presynaptic a2-adrenoceptors at the cortical serotoninergic axons.Send offprint requests to N. Limberger at the above address     

Effects of nitrendipine on the autoregulation of regional cerebral blood flow in the pithed rabbit

Summary Effects of the calcium-channel antagonist, nitrendipine, on the autoregulation of regional cerebral blood flow were studied by analysing the pressure-flow relationship in the cortex, subcortex and thalamus in pithed anesthetized rabbits. Arterial pressure was altered from 50 to 125 mm Hg by electrical stimulation of the spinal nerve roots. Regional blood flow was measured with the hydrogen clearance technique. Under control conditions, regional blood flow in the cortex, subcortex and thalamus did not change significantly within the range of mean arterial pressures of 50 to 100 mm Hg. Vascular resistance in each region rose significantly (P < 0.05) in a pressure-dependent manner. During the intravenous infusion of nitrendipine (0.3 and 1 g · kg^–1 · min^–1), blood flow to the three regions of the brain increased in a pressure-dependent manner when mean arterial pressure was increased from 50 to 125 mm Hg. The autoregulatory increase in regional vascular resistance was abolished. In addition, nitrendipine produced a blood pressure-dependent decrease of the vascular resistance in the subcortex and thalamus but not in the cortex. These results indicate that nitrendipine increases regional cerebral blood flows and suppresses regional autoregulations simultaneously. The autoregulatory adjustment in the cortex is more resistant to nitrendipine than that in the subcortex and thalamus. The observation that the action of nitrendipine was not the same in the three brain regions may be due to the vascular beds of these regions differing in their calciumchannel equipment.     

Presynaptic action of adrenaline on adrenoceptors modulating stimulation-evoked 3H-noradrenaline release from rabbit isolated aorta

Summary The purpose of this investigation was to study the effect of adrenaline on presynaptic adrenoceptors by recording the release of ³H-noradrenaline evoked by electrical-field stimulation. Adrenaline (10^–10–³ × 10^–9 mol/l) had no effect on the ³H-overflow evoked by stimulation of aorta preloaded with ³H-noradrenaline. At 10^–8 and 3 × 10^–8 mol/l, the ³H-overflow was decreased by up to 47%. The maximum decrease was more marked in the presence of either cocaine (3 × 10^–5 mol/l) plus corticosterone (4 × 10^–5 mol/l), cocaine (3.3 × 10^–6 mol/l) plus normetanephrine (4 × 10^–5 mol/l), or desipramine (10^–6 mol/l) plus normetanephrine (10^–5 mol/l). The relationship between adrenaline-induced decrease and stimulation-frequency was dependent on the experimental design: either the decrease was the same at all frequencies (1–16 Hz) or it was more marked, the lower the frequency (1 > 3 > 8 Hz). Phentolamine and rauwolscine (both 10^–6 mol/l) antagonized the inhibitory effect of adrenaline (10 ^{– 8}–10^–6 mol/l). Phenoxybenzamine (10^–6 mol/l), prevented the inhibitory effect. No enhancing effect of adrenaline (10^–9–10^–6 mol/l) was observed in the presence of these three -adrenoceptor antagonists. Our results suggest that adrenaline activates inhibitory ₂-adrenoceptors, but not facilitatory -adrenoceptors on postganglionic sympathetic nerve terminals in rabbit aorta. Send offprint requests to J. Abrahamsen at the above address