Pre- and postjunctional beta-adrenoceptor mediated effects on transmitter release and effector response in the isolated rat portal vein

Pre- and postjunctional control mechanisms of the portal vein of spontaneously hypertensive rats (SHR) were characterized. Emphasis was placed on the influence of the presynaptic beta-adrenoceptor mediated mechanism for regulation of neuronal noradrenaline (NA) release (studied as tritium overflow) and its consequences for the contractile response under in vitro conditions. It was found that isoprenaline increased, whereas dl-propranolol decreased the release of neuronal NA during transmural nerve stimulation, while effector responses remained unaltered. d-Propranolol and the beta-1 selective adrenoceptor antagonist, metoprolol, did not affect these two variables. It is concluded that the presynaptic beta-adrenoceptors in the rat portal vein are mainly of the beta-2 type and mediate facilitation of neuronal transmitter release and that concomitant changes of the effector responses of this tissue are below the level of detection under the present experimental conditions.     

Hepatic portal vein infusion of glucose on sodium excretion in the rat

Anesthetized rats were prepared with catheters in the hepatic portal (HPV) and femoral (FEM) veins and in the bladder or ureters. In some experiments the left kidney was denervated. HPV infusion of 1 M glucose at 2 ml/h for 20 min increased Na excretion by the kidney when given as a second infusion. Bilateral cervical vagotomy eliminated the increase in Na excretion during glucose infusion and uncovered a delayed decrease in Na and K excretion. Renal denervation attenuated the increase in Na excretion to HPV glucose. FEM infusion of glucose had variable effects, increasing Na excretion only after vagotomy. The results are interpreted to suggest that central and vagal receptors tend to enhance Na excretion whereas splanchnic nerve afferents and humoral mediator(s) have the opposite effect.     

Neuronal and extraneuronal uptake of 3H-noradrenaline in rat portal vein in vitro

Rat portal veins were incubated with 3 different concentrations of ³H-l-noradrenaline (³H-I-NA) and the radioactive material retained in the tissue as well as that present in the postincubation medium was analyzed after a postincubation period in substrate-free medium. Inhibition of the neuronal amine uptake mechanism (by preincubation with LU 3–010) reduced the retention of radioactivity in the tissue more at low than at high substrate concentrations. At increasing substrate concentrations the relative role of the extraneuronal amine uptake was increased. Corticosterone and hydrocortisone reduced extraneuronal accumulation whereas betametasone and methylprednisolone in the concentrations used were ineffective, indicating that the inhibition of extraneuronal uptake by the corticosteroids is unrelated to their glucocorticoid potency. When the composition of the retained radioactivity was analyzed, NA was found to be the major component of the retained radioactivity after inhibition of extraneuronal uptake, whereas tritiated catabolites were found to be the predominating constituent of the retained radioactivity after neuronal uptake inhibition. The possible role of inactivation of the adrenergic transmitter by the extraneuronal uptake mechanism in different situations is discussed.     

Oxygen dependence and energy turnover in normal and hypertrophic rat portal vein

Oxygen consumption (J₀₂), lactate production (J_LA), and active force were studied on rat portal veins that had hypertrophied in response to a 5 days period of increased transmural pressure. The vessels were mounted in vitro at optimum lengths for force development. The walls of the hypertrophic (H) veins had in comparison to their controls (C) an increased cross-sectional area (1.14plusmn;0.05 vs. 0.46±0.03 mm², S.E., n= 12). The H veins had a diminished or absent spontaneous contractile activity in contrast to C. The influence of surrounding P_O2 on amplitude of K⁺-induced contractures was studied in an open organ bath. For both Cand H veins a decline in force was seen at P_O2levels around 275 mmHgand below. Energy metabolism was studied in a closed glass chamber (volume 1.2 ml) at a P_O2of 290 mmHg. In comparison to recordings at 690 mmHg, J_LA and active force were unaltered in both groups indicating a sufficient O₂ supply. For veins relaxed in Ca²⁺-free solution J_O2and J_LA were higher in H veins compared to C if expressed per unit vessel length (J_O2: 0.47±0.03 vs. 0.20±0.02, J_LA: 0.66±0.09 vs. 0.22±0.03 nmol/min×mm, n= 6). When the comparisons were made per unit weight J_O2 was similar, about 0.38 μmol/min×g whereas J_LA was higher in the H group (0.53±0.04 vs. 0.38±0.05 μmol/min×g). Contractures were elicited in high-K⁺solutions with varied amounts of Ca²⁺added. Maximal force per unit area was lower for H veins compared to C (9.5 ± 1.6 vs. 16.3±3.3 mN/mm²). For both groups J_O2 increased with active force. J_LA increased with force for C but was unaltered for H veins. The relation between calculated ATP production and force was less steep for H indicating a lower metabolic tension cost.     

Differential actions of exogenous and intracellular spermine on contractile activity in smooth muscle of rat portal vein

Effects of the naturally occurring polyamine spermine on electrical and contractile properties of the rat portal vein were studied. 1 mM spermine nearly abolished spike activity and spontaneous contractions and decreased the intracellular Ca²⁺ concentration ([Ca²⁺],). The phasic force responses to 0.1 and 1 μM phenylephrine were partially inhibited, but not the sustain plateau contraction caused by 5 /IM phenylephrine. The Ca²⁺-force relation in high-K⁺ (128 mM)-depolarized veins was shifted to the right, EC₅₀ for Ca²⁺ increasing from 0.50 ± 0.03 mM (control, n= 8) to 0.65 ± 0.06 and to 0.94 ± 0.03 at 1 (n – 4) and 10 (n = 3) mM spermine, respectively. However, at a Ca²⁺ concentration of 2.5 mM, giving maximal force, there was no effect of spermine (1 mM) on either force or [Ca²⁺],. Whereas extracellular spermine thus reduced contractile activity at moderate levels of stimulation, increased intracellular concentration of spermine potentiated the force response to Ca²⁺. Intracellular loading of spermine by reversible permeabilization increased its concentration by 2–3 times. The spontaneous activity and response to phenylephrine were unchanged. However, the Ca²⁺-force relation of depolarized veins was shifted to the left, EC₅₀ decreasing from 0.51 ± 0.04 mM in controls (n= 7) to 0.36 ± 0.02 mM in the loaded veins (n= 9). Spermine increased Ca²⁺-activated force in portal veins permeabilized with β-escin. The degree of potentiation was consistent with observed effects in spermine-loaded intact veins. The results suggest that spermine at physiological intracellular concentration may contribute to the determination of Ca²⁺ sensitivity in vascular smooth muscle cells.     

基于冠状面数据的肝静脉和肝内门静脉的三维重建

目的:构建基于肝连续薄层冠状断面数据集的肝静脉和肝内门静脉的三维数字化可视模型。方法:应用数控冷冻铣削技术获取1例肝的连续薄层冠状断面数据集;采用体绘制和面绘制的方法,通过人工干预对数据集中肝内管道系统进行人工识别提取和图像数据分割;运用3D医学可视化软件实现三维重建,构建肝静脉和肝内门静脉的三维可视化模型。结果:肝静脉和肝内门静脉的可视化模型可清晰显示门静脉及其分支和肝静脉及其属支的空间构形,真实地再现了肝门静脉和肝静脉之间复杂的空间毗邻关系。模型中的肝静脉和肝门静脉可单独或总体显示,可在三维空间位置上绕任意轴旋转任意角度,并能从不同的角度对某一血管分支进行多角度、多方位的观察。结论:高质量的二维图像、精确的数据分割和合适的三维重建方法保证了三维数字化可视模型的真实性和准确性。     

人与猪肝门静脉生物力学特性的比较研究

目的：比较研究人与猪肝门静脉生物力学特性的异同，为猪→人异种肝移植提供理论依据。方法：取人与不同月龄猪肝门静脉，利用软组织生物力学试验机测量压力一直径关系数据，推导出其弹性模量和顺应性。结果：猪肝门静脉的弹性模量随月龄的增大和血管内压力的升高而增大；顺应性则随月龄的增大而下降。与人肝门静脉相比，6月龄猪肝门静脉的弹性模量和顺应性与人相近。结论：6月龄猪肝门静脉的力学特性与成人相近，在行猪→人异种肝移植时，人与6月龄猪肝门静脉的吻合是可行的。     

Mechanisms of endothelin-induced augmentation of the electrical and mechanical activity in rat portal vein

Actions of porcine endothelin (ET) on the electrical and mechanical activity of the rat portal vein were investigated by means of the intracellular microelectrode and isometric tension recording techniques, ET (> 0.1 nM) enhanced the amplitude and frequency of the spontaneous contractions which ceased in the presence of 100 nM dihydropyridine derivatives (nifedipine or nicardipine). ET (0.15 nM) increased the frequency of the spontaneous action potentials, with no change in the basal membrane potential. Higher concentrations of ET (≧ 0.3 nM) further depolarized the membrane potential and increased the spike frequency. After blocking the spontaneous action potentials with nifedipine (100 nM), ET still depolarized the membrane. The depolarization was associated with a reduction in the electrotonic potential and was blocked in a Na-deficient solution (15.5 mM) but not in Ca-free, K-deficient or Cl-deficient solutions. In a Na-deficient solution, ET still evoked action potentials without depolarization. In Ca-free solution, ET depolarized the membrane potential with small oscillations, which were blocked by nifedipine (100 nM). The results indicate that in the rat portal vein, ET enhances electrical and mechanical responses through activation of the dihydropyridine-sensitive and voltage-dependent Ca channels. Acceleration of the Ca entry induced by ET can occur with or without depolarization of the membrane and can enhance the pacemaking mechanism.     

The role of prostaglandins in the alpha- and beta-adrenoceptor mediated renin release response to graded renal nerve stimulation

The role of prostaglandins in the renin release response to renal nerve stimulation (RNS) at different intensities was examined in the anaesthetized dog. The animals were divided into two groups receiving either low or high level RNS, defined by the frequencies of stimulation producing reduction in renal blood flow by 5% or less and 50%. Indomethacin or diclofenac sodium (5 mg/kg i.v.), prostaglandin synthesis inhibitors, did not affect the renin release response to high level RNS by 31±8% (P<0.01). Addition of metoprolol, (0.5 mg/kg i.v.) beta-1-adrenoceptor antagonist, to indomethacin or diclofenac sodium resulted in a greater reduction (68±6%P<0.01) of the renin release response to high level RNS compared to that produced by either drug alone. Metoprolol, alone, reduced the renin release response to high level RNS by 37±14% (P<0.05). Phenoxybenzamine (0.6 g·kg^–1·min^–1), alphaadrenoceptor antagonist, into the renal artery practically abolished the renal vasoconstrictor response to high level RNS and reduced the renin release response by 50±7% (P<0.01). Addition of metoprolol to phenoxybenzamine practically abolished the renal vasoconstrictor response and the renin release response to high level RNS; 94±4% (P<0.01). Addition of phenoxybenzamine to indomethacin or diclofenac sodium practically abolished the renal vasoconstrictor response to high level RNS but did not produce any greater reduction of the renin release response than that produced by either drug alone. These findings suggest that low level RNS results in renin release which is not dependent on prostaglandins. High level RNS results in renin release which is partly mediated by beta-1-adrenoceptors and partly related to alpha-adrenoceptor mediated renal vasoconstriction. Prostaglandins are not involved in the beta-adrenoceptor mediated renin release but are involved in the renin release deriving from alpha-adrenoceptor mediated renal vasoconstriction.     

Structural and functional ontogenetic development of the rat portal vein after neonatal 6-hydroxydopamine treatment

The importance of the adrenergic vasomotor nerve supply for the vascular ontogenetic development has been studied in the isolated portal vein preparation from rats, at 5–6 weeks of age, who had either been chemically sympathectomized by a series of postnatal 6-hydroxydopamine (6-OHDA) injections or been receiving the solvent alone. It was found that 6-OHDA treatment largely, but not completely, prevented the outgrowth of the terminal NA fluorescent ground plexus. Nevertheless, the media underwent a seemingly normal differentiation into two layers. Functionally, the portal vein from the 6-OHDA treated animals displayed weak and non-persistent myogenic spontaneous activity; sensitivity to exogenous noradrenaline (NA) was increased 3-fold and maximum stress was increased by 25 % as compared to control. Responses to transmural field stimulation were only obtained at high impulse rates and the maximum response was attenuated. Considering the very sparse adrenergic innervation following 6-OHDA they seemed surprisingly large, however, but since they were abolished by tetrodotoxin and by phenoxybenzamine responses are concluded to be neurogenic and adrenergic in origin. A singular attenuation of neurogenic responses by atropine was found in 6-OHDA treated vessels but not in controls. It is concluded that the adrenergic vasomotor nerve supply seems to exert some trophic influence during ontogenetic development but that the morphologic vascular development is largely governed by other, non-neurogenic mechanisms. As to functional development, 6-OHDA induced sympathectomy causes impaired development of phasic myogenic activity whereas maximum stress is augmented as is the tissue sensitivity to exogenous NA.     

人与猪肝门静脉壁的细胞核密度的形态定量比较研究

目的比较研究人与猪肝门静脉细胞核密度间的异同,为猪与人异种肝移植提供理论依据。方法取人与不同月龄猪肝门静脉,常规有蜡包埋、切片,苏术精-伊红染色,桔黄G染平滑肌,光镜观察及计算机图像分析。结果猪肝静脉壁的细胞核数密度、面密度均随月龄的增加而降低。6月龄猪肝门静脉壁的细胞核数密度、面密度与人相近。结论猪肝门静脉壁的细胞核数密度、面密度随增龄发生变化,在行猪→人异种肝移植时,人与6月龄猪肝门静脉的吻合是可行的。     

肝纤维化门静脉压力改变与血清ET-1/NO关系的实验研究

目的制作兔肝纤维化模型，观察血管活性物质与门静脉压力变化的关系。方法40只家兔采用口服硫代乙酰胺方法造模，分别于造模第8、12、16、20周时检测内皮素（ET-1）及NO浓度，超声观察胆囊壁及肝脏血流动力学指标，直接穿刺测量不同时期门静脉压力。分析血管活性物质与肝脏血流动力学指标及门静脉压力变化间的关系。结果胆囊壁增厚是肝纤维化阶段的二维超声表现；随着纤维化程度的加重，血清ET-1、NO浓度逐渐增加，且以ET-1／N0比值增加更为明显；门静脉内压力、肠系膜上动脉、脾动脉搏动指数（PI）随纤维化程度逐渐增加，实验组与对照组间差异有统计学意义（P〈0．05），且与ET-1／NO值呈正相关（P〈0．01）。结论通过超声可无创检测肝脏血流动力学变化，对肝纤维化临床诊断及治疗效果的观察，具有积极的作用。     

Prognostic importance of some clinical and therapeutic factors for the effect of portal vein embolization in patients with primarily inoperable colorectal liver metastases

Introduction

Portal vein embolization (PVE) may increase the resectability of liver metastases. However, the problem of PVE is insufficient growth of the liver or tumor progression in some patients. The aim of this study was to evaluate the significance of commonly available clinical factors for the result of PVE.

Material and methods

Portal vein embolization was performed in 38 patients with colorectal liver metastases. Effects of age, gender, time between PVE and liver resection, oncological therapy after PVE, indocyanine green retention rate test, synchronous, metachronous and extrahepatic metastases, liver volume before and after PVE, increase of liver volume after PVE and the quality of liver parenchyma before PVE on the result of PVE were evaluated.

Results

Liver resection was performed in 23 (62.2%) patients within 1.3 ±0.4 months after PVE. Tumor progression occurred in 9 (23.7%) patients and 6 (15.8%) patients had insufficient liver hypertrophy. Significant clinical factors of PVE failure were number of liver metastases (cut-off – 4; odds ratio – 4.7; p < 0.03), liver volume after PVE (cut-off 1000 cm³; odds ratio – 5.1; p < 0.02), growth of liver volume after PVE (cut-off 150 cm³; odds ratio – 18.7; p < 0.002), oncological therapy administered concomitantly with PVE (p < 0.003).

Conclusions

Negative clinical factors of resectability of colorectal cancer liver metastases after PVE included more than four liver metastases, liver volume after PVE < 1000 cm³, growth of the contralateral lobe by less than 150 cm³ and concurrent oncological therapy.     

A comparison of the effects of intracellular and extracellular pH on contraction in isolated rat portal vein.

1. The effects of changes in extracellular and intracellular pH on spontaneous contractile activity in isolated rat portal vein have been investigated. 2. Small strips of portal vein were loaded with the pH-sensitive fluorophore carboxy-SNARF and intracellular pH (pHi) and contraction were measured simultaneously at 37 degrees C. The tissue was superfused with oxygenated, Hepes-buffered solutions at pH 7.4. Intracellular pH was altered by isosmotic substitution of weak acids or bases. External pH (pHo) was altered by addition of strong acid or base to the solution. 3. The mean resting value of pHi was 7.06 +/- 0.03 (n = 28). Alteration of pHi led to changes in spontaneous activity. Addition of butyrate (20 mM) reduced pHi by 0.18 +/- 0.01 pH units (n = 8). Decreasing pHi produced an early, brief increase in contractile activity followed by a longer lasting decrease or even abolition of contraction. 4. Addition of 20 mM trimethylamine or NH4Cl increased pHi by around 0.2 pH units and produced an early transient decrease in contractile activity followed by a later maintained increase, both in frequency and magnitude. Removal of base produced a rapid rebound decrease in pHi which was associated with a further transient increase in contractile activity followed by decreased activity. The effects of base on both pHi and contraction were concentration dependent over the range investigated (2.5-30 mM). 5. Alteration of pHo produced a change in pHi in the portal vein. The pHi change was rapid compared to other non-vascular cells (about 1 min to half-maximal response).(ABSTRACT TRUNCATED AT 250 WORDS)     

VIP inhibition of vascular smooth muscle: complementary to β2-adrenoceptor mediated relaxation in the isolated rat portal vein

Exogenous VIP caused a concentration dependent inhibition of the spontaneous mechanical activity in the isolated rat mesenteric-portal vein preparation via a mechanism which was completely independent of the propranolol-blocked β-adrenoceptor, of high K⁺ in the medium and of exogenous bovine pancreatic polypeptide, neurotensin and opioids. The potency of VIP ((pD₂=7.52±0.18, n=6) was about 30 times higher than that of isoprenaline in the atropine and phentolamine-blocked preparation. The isoprenaline inhibition was mediated via a β₂-type of adrenoceptor with low apparent affinity for noradrenaline (intrinsic activity (a) = 0.27±0.01, n=8). Opposite effects of exogenous VIP and noradrenaline were on the other hand observed in the atropinized and β-blocked preparation. These results suggest that in the rat portal vein neuronal VIP and circulating adrenaline may be complementary in their antagonism of the α-adrenoceptor mediated increase in contractility.     

Different effects of typical and atypical neuroleptics on K+-stimulated dopamine release from isolated rat striatum

Laboratory of Neurochemical Pharmacology, Research Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 7, pp. 47–49, July, 1992.