中枢和外周脑钠素(BNP)调节醛固酮分泌的不同作用

将BNP和AT-Ⅱ、ACTH AVP单独或BNP与这3种肽分别合并在大鼠icv或iv注入后观察血Ald浓度的变化。实验结果表明:①iv给予AVP(5μg/3ml·h~(-1))、ACTH(5μg/3ml·h~(-1))和AT-Ⅱ(5 v.g/3 ml·h(-1)),1h后均能增加血Ald的浓度。iv给予BNP(5μg/3ml·h(-1))能明显抑制AVP和ACTH的刺激作用,而不影响AT-Ⅱ的刺激作用。②icv给予BNP(2 Vg/10 pl NS)能降低血Aid浓度。icv给予AVP(2μg/10μl NS)能增加血Aid浓度,但ACTH(2μg/10μl NS)和AT-Ⅱ(2μg/10μl NS)无此种作用。但如脑室同时给予BNP(2μg/10μlNS)却可明显刺激Aid分泌。③icv注入BNP对外周注入的3种多肽的刺激作用无任何影响。从上述的实验结果可看出:脑内BNP可“反常”地增加AT-Ⅱ、ACTH和AVP对Ald分泌的刺激作用,与外周抑制AVP,ACTH的刺激作用不同。而脑内BNP不影响这3种多肽的外周刺激作用。结论是脑内BNP以其独特的方式调节Ald的分泌,控制水盐代谢。     

Plasma atrial natriuretic peptide (ANP) concentration and fluid balance during rapid intravenous saline infusions in camels

Human muscle samples were obtained with the percutaneous biopsy technique. The samples were membrane-hyperpermeabilized (skinned) using a chemical or freeze-drying technique. Short single fibre segments were dissected from the sample, transferred to an experimental chamber, connected to a force transducer and manipulator, and exposed to temperature-controlled solutions. The force generating-capacity, the sensitivity of the contractile apparatus to calcium and the caffeine threshold for calcium release from the sarcoplasmic reticulum could be studied in the short muscle fibre segments obtained from man with the percutaneous muscle biopsy technique. The average length of the fibre segments between the connectors was 0.44±0.21 mm. Thus, detailed studies of the contractile machinery can be made on human skinned muscle fibres with only minimal discomfort to the patient or subject during biopsy, which should be useful in studies of neuromuscular disease, muscle plasticity or in applied physiology.     

牛磺酸对高血压和血管活性物质的影响

在原发性高血压(EH)患者、大鼠腹主动脉狭窄和高盐摄入引起高血压模型上,观察到口服牛磺酸治疗4周后均明显降低平均动脉压和收缩压,42.2%的患者血压恢复正常,并能抑制EH患者和高血压大鼠血浆内皮素(ET)、血管紧张素II(AII)水平的升高,增加高血压大鼠血浆降钙素基因相关肽(CGRP)和主动脉组织中的牛磺酸含量.以上结果表明,牛磺酸在降压作用同时伴有缩血管物质的降低和舒血管物质的增加,为以牛磺酸作为降血压辅助药物提供了依据.     

体外培养新生大鼠心房壁中的CGRP-IR和NPY-IR神经细胞

对体外培养新生SD大鼠心房壁的神经细胞，按SternbergerPAP法进行了降钙素基因相关肽（CGRP）和神经肽Y（NPY）免疫细胞化学研究。结果显示：CGRP-IR阳性细胞数量较少，实验的5份标本只有2份见到阳性细胞，而NPY-IR阳性细胞在所有实验标本中均可见到。本研究在培养条件下证实心内神经节中有CGRP-IR阳性细胞存在，支持心脏有器官内感觉神经细胞的设想。同时对心内神经细胞的化学性质进行了讨论。     

Prostaglandins and CGRP release from cardiac sensory nerves

Summary (1) The possible influence of Prostaglandins (PG) E₁ and I₂ as well as ischaemia, ouabain and bradykinin on the outflow of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (LI) from the guinea-pig heart was studied in vitro. (2) Exposure to PGE₁ (10^–5 M), but not PGI₂ (10^–5 M), induced an increased outflow, suggesting release of CGRP-LI. PGE₁ simultaneously increased the contractile force and heart rate while no effects were observed on perfusate volume or outflow of NPY-LI. PGI₂ had no effect on contractile parameters or coronary flow. In separate experiments on capsaicin-pretreated animals, the stimulatory effects of PGE₁ on heart rate and contractile force remained unchanged while no increased CGRP-LI outflow was detectable. (3) Ouabain, bradykinin and reperfusion after total stop-flow ischaemia was associated with an indomethacin-resistant increase in perfusate levels of CGRP-LI but not of NPY-LI. While ouabain markedly increased the contractile force, exposure to bradykinin or ischaemia did not induce any clear-cut changes in contractile force or heart rate. (4) Capsaicin-exposure evoked a markedly increased outflow of CGRP-LI but not of NPY-LI in combination with an increase in heart rate and a decrease in contractile force. Repeated administration of capsaicin induced tachyphylaxis. The stimulatory effects of capsaicin on CGRP-LI outflow and heart rate, but not the negative inotropic effect, did not occur in capsaicin-pretreated animals. (5) It is concluded that PGE₁, but not PGI₂, can activate cardiac capsaicin-sensitive fibres as revealed by increased outflow of CGRP-LI. The cardiostimulatory effects induced by PGE₁ are not related to CGRP release, however. A possible prostaglandin link in the CGRP-LI released by ouabain, bradykinin or ischaemia seems unlikely. Send offprint requests to: A. Franco-Cereceda at the above address     

Early nerve regeneration after Achilles tendon rupture — a prerequisite for healing? A study in the rat

Nerve regeneration during healing of Achilles tendon rupture in the rat was studied by immunohistochemistry including semi-quantitative assessment. Neuronal markers for regenerating and mature fibers, ie., growth associated protein 43 (GAP-43) and protein gene product 9.5 (PGP 9.5), respectively, were analyzed at different time points (1-16 weeks) post-rupture. In the paratenon, both the ruptured and intact contralateral tendon (control) consistently exhibited immunoreactivity to the two neuronal markers. However, in the proper tendinous tissue only the ruptured tendon showed immunoreactivity to GAP-43 and PGP 9.5. This expression was seen already at week 1 post-rupture to reach a peak at week 6 followed by a successive drop till week 16. Also the occurrence of sensory and autonomic fibers according to immunoreactivity for calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY), respectively, was analyzed. CGRP-positivity was abundantly seen from weeks 2-6 in both perivascular and sprouting free nerve endings in the proper tendon tissue undergoing healing. NPY appeared later, at weeks 6-8 post-rupture around blood vessels mainly located in the surrounding loose connective tissue. Apart from a role in vasoaction (CGRP, vasodilatory; NPY, vasoconstrictory). both neuropeptides have been implicated in fibroblast and endothelial cell proliferation required for angiogenesis. The present study shows that early healing of ruptured tendons is characterized by an orchestrated, temporal appearance of nerve fibers expressing peptides with different actions. The observed pattern of neuronal regeneration and neuropeptide expression may prove to be important for normal connective tissue healing.     

Opioid peptides and receptors in joint tissues: study in the rat.

Using immunohistochemical and biochemical techniques, the occurrence of endogenous opioid peptides and their receptors in normal rat bone and joint tissues was investigated. Opioid receptors were detected, quantified, and characterized in homogenates from capsule/synovium and periosteum using radioligand binding assays. Receptor binding of the nonselective opioid [3H]naloxone to tissue homogenates was stereospecific and saturable, showing similar characteristics to that of brain tissue, although with lower binding capacities. By immunohistochemistry, the neuronal occurrence of four different enkephalins was demonstrated in synovium, bone marrow, periosteum, and juxta-articular bone, whereas no neuronal dynorphin immunoreactivity was detected. Double-staining studies disclosed that enkephalins coexisted with substance P in primary afferent fibers. The applied techniques can be used to assess changes in the distribution of endogenous opioids and their receptors in joint tissues in conditions associated with pain and inflammation. The endogenous opioid system now demonstrated might be targeted and exploited therapeutically to obtain peripheral control of symptoms in joint disorders.     

Enzyme-linked Immunosorbent Assay of Pro-gastrin-releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron-specific Enolase Measurement

Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.