脑内阿片肽在去甲肾上腺素中枢降压效应中的作用

本文分析大鼠侧脑室注射(icv)去甲肾上腺素(NE)和α受体激动剂可乐宁的心血管效应与脑内几种阿片肽的关系。实验用颈总动脉插管的麻醉动物完成。 一、侧脑室注射NE和可乐宁的降压效应及α阻断剂的预防作用:大鼠icv 10μg NE,引起降压和心率减慢反应,70分钟内血压与心率的最大降低百分数分别为-26±5     

U 50 488H 对高血压大鼠的利尿作用及机制

目的： 观察κ阿片受体激动剂U50 488H对自发性高血压大鼠（SHR）的利尿作用并探讨其作用机制。 方法： 用整体实验观察U50 488H对WKY大鼠和SHR血压和尿量的影响；应用放射免疫分析方法观察WKY大鼠和SHR血浆中体液因子的变化。 结果： U50 488H显著降低WKY大鼠和SHR的血压，对SHR产生的降压效应大于WKY大鼠；U50 488H剂量依赖性地引起WKY大鼠和SHR尿量的增加，而且对SHR的利尿作用强于WKY大鼠；测定血浆因子水平发现，U50 488H不仅能引起WKY大鼠和SHR血浆ADH水平的显著下降，并且对SHR血浆ADH水平的降低效应大于WKY大鼠；另外，U50 488H对WKY大鼠血浆AngⅡ水平无明显影响，但可以引起SHR血浆AngⅡ水平显著下降。U50 488H的以上效应均可被选择性κ阿片受体阻断剂nor-BNI所阻断。 结论： κ阿片受体激动剂U50 488H显著下调血浆中抗利尿激素和血管紧张素Ⅱ的水平可能与其引起SHR强利尿效应有关。     

NPY与NT在血液透析中的变化及其意义

采用放射免疫分析法检测３０例维持性血液透析（ＨＤ）患者ＨＤ过程中血浆ＮＰＹ与ＮＴ的含量，并以３０例正常人作为对照。结果显示：ＨＤ患者血浆ＮＰＹ与ＮＴ水平均显著增高（Ｐ〈０．０１）。与ＨＤ前比较，ＨＤ后ＮＰＹ水平明显下降（Ｐ〈０．０１）。ＮＴ水平则明显增高（Ｐ〈０．０１）。于ＨＤ １ｈ测得动脉血浆ＮＰＹ水平明显高于静脉血（Ｐ〈０．０１）。１９例ＨＤ高血压病人ＮＰＹ与ＮＴ水平均显著高于非高血压组（Ｐ〉     

脊髓内强啡肽在去甲肾上腺素中枢降压效应中的作用

本文分析大鼠脊髓蛛网膜下腔注射(ith)去甲肾上腺素(NE)和α受体激动剂可 乐宁的心血管效应与脊髓内阿片肽的关系。实验用颈总动脉和脊髓蛛网膜下腔导管植入的麻醉动物完成。结果如下: 一、阿片受体阻断剂纳洛酮对ith NE和可乐宁降压效应的预防作用:大鼠ith 10μg NE或1μg可乐宁引起明显的降血压和心率减慢作用。大剂量纳洛酮(100μg,ith     

血液透析前后血小板提取液中NPY与NT含量的变化及意义

探讨血液透析（ＨＤ）过程对慢性肾功能衰竭患者（ＣＲＦ）血小板中神经肽Ｙ（ＮＰＹ）与神经降压素（ＮＴ）含量的影响及ＮＰＹ 与ＮＴ 的作用机制。我们采用特异性放射免疫分析方法,对血小板提取液和不含血小板血浆中ＮＰＹ 及ＮＴ 含量进行ＨＤ 前后的动态观察,并以３０ 例健康人作为对照。结果：正常对照组提取的血小板液中ＮＰＹ 与ＮＴ 含量分别为（５８１８±２１２９） ｎｇ／１０９ 和（２５３８±１３４３） ｎｇ／１０９。与对照组比较,ＨＤ 前ＣＲＦ患者血小板提取液中ＮＰＹ 含量明显降低,ＮＴ 显著高于对照组。而ＨＤ后ＣＲＦ患者血小板提取液中ＮＰＹ 与ＨＤ 前比较明显增高,ＮＴ 则明显降低。ＣＲＦ患者血浆ＮＰＹ 含量在ＨＤ 前明显高于对照组,ＨＤ后明显下降。且ＮＰＹ 与ＮＴ 之间具有明显的相关性。结论：在ＣＲＦ病理过程中,由血小板释放的ＮＰＹ 和ＮＴ 与５羟色胺等生物活性物质共同参与了以缩血管效应为主的免疫反应,是造成肾性高血压和肾血管痉挛的重要病理因素。     

脊髓α肾上腺素能受体在血压调节中的作用

为了阐明脊髓α肾上腺素能受体在血压调节中的作用,我们在大鼠脊髓蛛网膜下腔注射α受体阻断剂酚妥拉明,观察其对血压调节功能的影响,结果如下: 1.脊髓蛛网膜下腔注射酚妥拉明引起大鼠血压明显下降:6例大鼠,脊髓蛛网膜下腔注射酚妥拉明30μg/10μl,结果平均动脉压下降27.2±14.4mmHg,P<0.01。     

中枢神经降压素对大鼠胃应激性溃疡的作用及多巴胺的关系

目的和方法：用双侧中央杏仁核微量注射等方法,观察中枢内神经降压素（ＮＴ）在大鼠束缚加水浸诱发的应激性胃溃疡中的作用及其与多巴胺（ＤＡ）的关系。结果：（１）双侧中央杏仁核内注射微量ＮＴ或ＤＡ可显著减轻水浸加束缚应激所诱发的胃粘膜损伤（Ｐ＜００１）;（２）双侧中央杏仁核内注射微量抗ＮＴ血清,可诱发非应激大鼠出现胃溃疡;（３）双侧中央杏仁核注射ＮＴ前,双侧中央杏仁核注射微量６－羟多巴胺（６－ＯＨＤＡ）或腹腔注射氟哌啶醇（ｈａｌ）均可逆转ＮＴ的胃粘膜保护作用。结论：中央杏仁核内ＮＴ对胃应激性溃疡的细胞保护作用主要是通过调节多巴胺能神经传递实现的。     

急性实验性低血压时针刺升压的机制

胡旭初等报道用静脉注射药物造成动物血压异常,针刺可使血压异常状态趋于正常化。我们证实针刺对清醒犬静脉匀速注射去甲肾上腺素造成的实验性高血压有显著的降压效应,此降压效应与电针时内源性鸦片样物质的释放和神经中枢内鸦片样受体的激活有关。本工作试图观察针刺对急性实验性低血压有无升压作用,并分析其机制。     

延髓头端腹外侧区微量注射异搏定和毒扁豆碱对大鼠血压和心率的影响

延髓头端腹外侧区(γVLM)在防御反应中是心血管活动调节的重要中枢,该处神经元具有高度整合功能,能影响交感紧张性与血压水平,但这个中枢所涉及的递质仍在研究中。本文采用微量注射法,观察了大鼠双侧γVLM微量注射异搏定和毒扁豆碱对动脉血压和心率的影响,结果表明微量注射毒扁豆碱后即刻引起动脉血压升高,心率增快;而微量注射毒扁豆碱之前先注射异搏定,动脉血压和心率仅轻度升高,两组升高的程度有明显差异(P<0.01,P<0.05),揭示异搏定可部分阻断毒扁豆碱的升压和心率加快效应。     

脊髓内去甲肾上腺素在心血管活动调节中的作用

关于中枢去甲肾上腺素(NE)在心血管活动调节中的作用,以往的研究多侧重于脑内。本文从脊髓水平进行了探讨。实验用颈总动脉和脊髓蛛网膜下腔植入导管的麻醉动物完成。结果如下: 一、脊髓蛛网膜下腔注射(ith)NE的降压效应:大鼠ith 2.5～10μgNE,引起与剂量相关的降血压(-9±2～-20±4％)与减慢心率(-5±4～-17±4％)作用。预先ithα阻断剂酚妥拉明、α_1阻断剂哌唑嗪或α_2阻     

Effect of neurotensin on contractile activity and [3H]acetylcholine release in cat terminal ileum during different postnatal periods.

The effect of neurotensin (NT) on the contractile activity of circular and longitudinal strips from the terminal ileum of 15-, 30-, 60-day-old and adult cats as well as on the resting and electrically-evoked release of [3H]acetylcholine (ACh) was studied. Radioactivity was measured by liquid scintillation spectrometry and the effect of NT was evaluated by the S2/S1 ratio. In the circular muscle strips NT (1-100 nM) inhibited spontaneous contractions in all age groups. In the longitudinal strips the effect of NT was concentration- and age-dependent. NT at a concentration of 1 nM had no effect on the spontaneous activity in 15-day-old cats, but in the other age groups in 70-80% of the cats it inhibited spontaneous contractions. The response to 10 and 100 nM NT was either biphasic (relaxation followed by contraction) or inhibitory: in 15-day-old cats the response was biphasic only and with increasing age the percentage of strips responding with inhibition of the contractions increased. Neither substances affecting adrenergic and cholinergic transmission nor TTX changed the inhibitory response to NT. The contractile component of the biphasic response was TTX-resistant in all age groups and was significantly decreased by scopolamine in 60-day-old and adult cats. NT increased both resting and electrically-evoked release of [3H]ACh which was not changed by TTX. In the presence of the peptide the S2/S1 ratio increased as NT-induced [3H]ACh release in the strips of adult cats was higher than that in young cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

GABA may function tonically via GABA(A) receptors to inhibit hypotension and bradycardia by L-DOPA microinjected into depressor sites of the nucleus tractus solitarii in anesthetized rats

We have proposed that DOPA is a transmitter of the primary baroreceptor afferents terminating in the rat nucleus tractus solitarii (NTS). GABA is a putative inhibitory neuromodulator for baroreflex inputs in the NTS. GABA may inhibit DOPAergic transmission. Drugs were microinjected into depressor sites of the NTS in anesthetized rats. DOPA (10-60 ng) elicited dose-dependent depressor responses. GABA (3-300 ng) elicited dose-dependent pressor responses. Nipecotic acid (100 ng) elicited pressor responses. Bicuculline (10 ng) elicited depressor responses. Responses to DOPA (30 ng) were inhibited by pretreatment with GABA and nipecotic acid, but potentiated by bicuculline, when vascular responses to pretreated drugs returned to basal levels. DOPA ME, a competitive DOPA antagonist, did not displace specific [3H]GABA binding. Prior DOPA ME (1 microg) inhibited by one-half pressor responses to 300 ng GABA. GABA seems to inhibit tonically via GABA(A) receptors depressor responses to DOPA and to elicit pressor responses partially by inhibition of tonic function of endogenous DOPA to activate depressor sites in the NTS. These findings further support the above proposal.     

Participation of capsaicin-sensitive afferent neurons in gastric motor inhibition caused by laparotomy and intraperitoneal acid.

Stimulation of somatic or visceral nociceptors causes changes in gastrointestinal motor activity and blood pressure. The present study examined the possible participation of capsaicin-sensitive afferent and noradrenergic efferent neurons in the blood pressure and gastric motor responses to laparotomy and intraperitoneal injection of capsaicin or hydrochloric acid in the rat. Gastric motor activity was measured by recording the intragastric pressure of phenobarbital-anaesthetized rats via an oesophageal catheter. Laparotomy as well as intraperitoneal injection of capsaicin (33 and 330 microM) or hydrochloric acid (30 mM) caused a transient reduction of gastric motor activity stimulated by intravenous infusion of bombesin (200 pmol/min) and a brief fall of blood pressure (depressor effect). The depressor effect of laparotomy was followed by prolonged hypertension. Defunctionalization of capsaicin-sensitive afferent neurons by systemic pretreatment of rats with capsaicin (0.4 mmol/kg) prevented the depressor effect and gastric motor inhibition elicited by laparotomy, intraperitoneal capsaicin (33 microM) or intraperitoneal hydrochloric acid (30 mM). However, the effects of 330 microM capsaicin on blood pressure and gastric motility were only partially reduced by capsaicin pretreatment. Blockade of noradrenergic sympathetic neurons by pretreating rats with guanethidine (0.225 mmol/kg) prevented the gastric motor inhibition and depressor effects of laparotomy and intraperitoneal injection of hydrochloric acid (30 mM). The inhibition of gastric motility caused by capsaicin (33 and 330 microM) was only partially reduced by guanethidine pretreatment. The secondary hypertension following the depressor effect of intraperitoneal capsaicin or hydrochloric acid was enhanced in guanethidine-pretreated rats whereas the prolonged hypertension induced by laparotomy was left unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of neurotensin on electrical and mechanical properties of smooth muscles in longitudinal and circular layers of the guinea-pig ileum

Effects of neurotensin (NT) on the electrical and mechanical activities of longitudinal and circular muscles of the guinea-pig ileum were investigated using the micro-electrode and isometric tension recording methods. In longitudinal muscles, the resting membrane potential was not affected by NT (0.1–30 nmol/l), but NT did provoke the contraction when applied in concentrations over 1 nmol/l. TTX (0.1 mol/l) neither modified the resting membrane potential nor the contraction evoked by NT, under condition of pretreatment with - and -adrenoceptor blockers. In circular muscles, NT (over 0.1 nmol/l) consistently hyperpolarized the membrane and increased the ionic conductance. The hyperpolarization appeared with a transient hyperpolarization, which gradually declined with a long time course. Using apamin and various concentrations of Ca, the NT-induced hyperpolarization was classified into two subtypes; fast and slow. The former was composed of maximum hyperpolarization due to activations of the Ca independent K channel, and the latter was composed of late hyperpolarization, due to activations of the Ca dependent K channel. During the NT-induced hyperpolarization in circular muscles, the amplitude of non-adrenergic, noncholinergic inhibitory junction potential (i.j.p.) evoked by field stimulation was reduced. This reduction induced by 0.5 nmol/l NT was mainly due to hyperpolarization of the membrane, and that observed in a high concentration of NT (3 nmol/l) was directly involved in ionic mechanisms contributing to the generation of i.j.p. In circular muscles, NT (over 3 nmol/l) did relax the tissue pre-contracted with 17.8 mmol/l K, but NT (below 30 nmol/l) did not relax the tissue pre-contracted by 39.6 mmol/l K. The relaxation of the pre-contracted tissue induced by NT depended on the hyperpolarization induced by NT. The results indicate that NT has direct actions on muscle cells of both longitudinal and circular layers of the ileum. In longitudinal muscles, NT has no effect on the membrane potential but does produce contraction, while in circular muscles, NT activates the Ca independent and Ca dependent K channels and relaxes the tissue, by hyperpolarizing the membrane. The membrane response evoked by NT differs from that induced by the activation of non-adrenergic, non-cholinergic nerves.     

L-dopaergic components in the caudal ventrolateral medulla in baroreflex neurotransmission.

L-3,4-Dihydroxyphenylalanine (L-DOPA) is probably a transmitter of the primary baroreceptor afferents terminating in the nucleus tractus solitarii; L-DOPA functions tonically to activate depressor sites of the caudal ventrolateral medulla, which receives input from the nucleus tractus solitarii [Misu Y. et al. (1996) Prog. Neurobiol. 49, 415-454]. We have attempted to clarify whether or not L-DOPAergic components within the caudal ventrolateral medulla are involved in baroreflex neurotransmission in anesthetized rats. Electrolytic lesions of the right nucleus tractus solitarii (1 mA d.c. for 10 s, 10 days before measurement) selectively decreased by 45% the tissue content of L-DOPA in the dissected ipsilateral caudal ventrolateral medulla. Electrolytic lesions did not decrease dopamine, norepinephrine and epinephrine levels. During microdialysis of the right caudal ventrolateral medulla, extracellular levels of L-DOPA, norepinephrine, epinephrine and 3,4-dihydroxyphenylacetic acid were consistently detectable using high-performance liquid chromatography with electrochemical detection. However, extracellular dopamine levels were lower than the assay limit. Baroreceptor activation by i.v. phenylephrine selectively evoked L-DOPA without increasing the levels of norepinephrine, epinephrine and 3,4-dihydroxyphenylacetic acid. This L-DOPA release was suppressed by acute lesion in the ipsilateral nucleus tractus solitarii. Intermittent stimulation of the right aortic depressor nerve (20 Hz, 3 V, 0.3 ms duration, for 30 min) repetitively and constantly caused L-DOPA release, hypotension and bradycardia, without increases in levels of norepinephrine, epinephrine and 3,4-dihydroxyphenylacetic acid. Local inhibition of L-DOPA synthesis with alpha-methyl-p-tyrosine (30 microM) infused into the ipsilateral caudal ventrolateral medulla gradually decreased basal levels of L-DOPA and 3,4-dihydroxyphenylacetic acid without decreasing norepinephrine and epinephrine. The inhibition of L-DOPA synthesis interrupted L-DOPA release and decreased by 65% depressor responses elicited by aortic nerve stimulation; however, it produced no effect on bradycardic responses. CoCl2 (119 ng), a mainly presynaptic inhibitory transmission marker, and L-DOPA methyl ester (1 microg), a competitive L-DOPA antagonist, when microinjected into depressor sites of the right caudal ventrolateral medulla, reduced by 60% depressor responses to transient ipsilateral stimulation of the aortic nerve (20 Hz, 3 V, 0.1 ms duration, for 10 s). No changes in bradycardic responses were observed. There may exist an L-DOPAergic relay from the nucleus tractus solitarii to the caudal ventrolateral medulla. L-DOPAergic components in the caudal ventrolateral medulla are involved in baroreflex neurotransmission via a baroreceptor-aortic depressor nerve-nucleus tractus solitarii-caudal ventrolateral medulla relay in the rat.     

Systemic hypertension after kidney transplantation: associated risk factors and influence on graft survival

Systemic hypertension after kidney transplant (HAPT) has been associated with a reduction in graft survival and increased morbidity and mortality of kidney transplant recipients. With the use of calcinuerin inhibitors, prevalence of HAPT has increased to 60-80%. The purpose of this study was to document the prevalence of HAPT in kidney transplant recipients attending the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" associated risk factors and the effect of hypertension in long term graft survival. We retrospectively reviewed the clinical charts of all the patients that underwent kidney transplant from 1984 to 1994. The following risk factors were studied: age, gender, cause of renal failure, presence of hypertension before kidney transplant, histocompatibility, acute rejection episodes, chronic rejection, serum creatinine values and use of cyclosporine. We divided subjects in two groups: normotensive (NT) and hypertensive (HT). HAPT included 3140/90 mmHg blood pressure level observed at least during two consecutive evaluations or the use of antihypertensive medication. We analyzed 215 grafts from 205 patients (10 patients had two kidney transplants); mean age at transplant of 30 +/- 9 years, 131 subjects were female and 84 male. One hundred and eighty eight patients (88%) displayed pretransplant hypertension. The mean follow up was 56+/-32 months. In the postransplant period 152 (71%) were HT and 63 (29%) NT. The HT group had significantly higher blood pressure and serum creatinine values than the NT group (P < 0.001), in spite of an adequate blood pressure control in 65% of the patients from the HT group. The NT group displayed a higher graft survival than the HT group; 60 +/- 30 months vs. 51 +/- 32 months respectively (p<0.01). Multivariate analysis did not show any risk factors independently associated with the development of HAPT. The prevalence of HAPT in our series is similar to the one reported in the literature. During the postransplant period there was a reduction of hypertensive patients (88% pretransplant vs. 71% postransplant). HAPT is a significant risk factor associated with long term survival of the graft.     

Involvement of nitric oxide production via kynurenic acid-sensitive glutamate receptors in DOPA-induced depressor responses in the nucleus tractus solitarii of anesthetized rats

We have proposed the hypothesis that L-3,4-dihydroxyphenylalanine (DOPA) plays a role of neurotransmitter of the primary baroreceptor afferents terminating in the nucleus tractus solitarii (NTS). In the present study, we tried to clarify whether glutamate receptors and/or nitric oxide (NO), important modulators for central cardiovascular regulation, are involved in the DOPA-induced cardiovascular responses in the nucleus. Male Wistar rats were anesthetized with urethane and artificially ventilated. Compounds or antisense oligos (17-mer) for neuronal NO synthase were microinjected into depressor sites of the unilateral nucleus. DOPA 30-300 pmol microinjected into the nucleus dose-dependently induced depressor and bradycardic responses. Prior injection of kynurenic acid (600 pmol) suppressed DOPA (300 pmol)-induced responses by approximately 80%. Prior injection of N(G)-monomethyl-L-arginine 100 nmol, a potent NO synthase inhibitor, reversibly attenuated by approximately 90% DOPA-induced responses, while the D-isomer 100 nmol produced no effect. Furthermore, prior injection of neuronal NO synthase antisense oligos (20 pmol) reversibly reduced by approximately 70% responses to DOPA. Sense or scrambled oligos produced no effect. A NO precursor L-arginine (30 nmol) induced depressor and bradycardic responses, but these responses were not affected by kynurenic acid. These results suggest important roles for glutamate receptors and NO in DOPA induced-depressor and bradycardic responses in the NTS.     

Neurotensin-induced excitation of neurons of the rat's frontal cortex studied intracellularly in vitro

Summary The actions of neurotensin (NT) on frontal pyramidal neurons were studied in vitro in slices of rat cerebral cortex using current clamp and single electrode voltage clamp (SEVC) techniques. Bath application of NT (0.1 M–10 M) induced a depolarization (2–13 mV) in 88% of the pyramidal cells, this effect was associated with a decrease in input conductance of 5–35% and its reversal potential was estimated at -88 +/-9.7mV. Typically, this depolarizing effect of NT was transient, since no cell responded to a second application of the peptide within 20 min after the first one. NT also induced an increase in the rate of firing of pyramidal cells evoked by direct stimulation, even when an hyperpolarizing current was applied to prevent the depolarization induced by NT. This effect could neither be explained by a decrease of the post-spike after-hyperpolarization, nor by an increase of the persistent sodium current which sustains the spiking of pyramidal cells, since the former was not affected consistently by NT and the later was insensitive to the peptide. This excitation of pyramidal neurons by NT persisted after blockade of synaptic transmission. On the other hand, NT also enhanced the synaptic noise recorded in pyramidal cells in standard perfusing medium. Furthermore, dopaminergic antagonists and noradrenergic antagonists failed to block these effects of NT. Finally, the inactive fragment of the peptide, NT(1–8), did not affect membrane properties of pyramidal cells. All together, these results suggest that NT excites frontal cortical neurons through the activation of specific NT receptors.     

Activation of brainstem endorphinergic neurons causes cardiovascular depression and facilitates baroreflex bradycardia

The effects of electrical stimulation of the arcuate nucleus on blood pressure, heart rate and baroreflex sensitivity were studied in urethane-anesthetized Sprague-Dawley rats. Stimulation of the mid-anterior parts of the arcuate nucleus at 80 Hz, 0.8 ms and 50-200 microA caused a biphasic, depressor/pressor, response and moderate bradycardia. Intravenous administration of a vasopressin V1-receptor antagonist eliminated the pressor component and unmasked a pure depressor response. This depressor response could be inhibited by naltrexone, 2 mg/kg i.v., by an antiserum against beta-endorphin, 100 nl injected directly into the ipsilateral nucleus tractus solitarii, or by deafferentation of the dorsal vagal complex (nucleus tractus solitarii and dorsal vagal nucleus) by an ipsilateral, dorsolateral knife-cut of the medulla oblongata. Stimulation of the arcuate nucleus at currents of 20-40 microA did not influence basal blood pressure or heart rate but potentiated the reflex bradycardia induced by phenylephrine, and this effect was completely blocked by naltrexone. It is concluded that a beta-endorphin-containing pathway projecting from the arcuate nucleus to the ipsilateral dorsal vagal complex is involved in depressor cardiovascular regulation and in the facilitation of baroreflex bradycardia.