偏头痛患者血浆的一氧化氮含量的研究

目的:为了探讨NO与偏头痛的关系。方法:采用比色法测定62例偏头痛患者血浆NO的含量。结果:偏头痛患者发作期血浆NO含量明显低于正常对照组,间歇期与正常对照组比较无差异。结论:NO可能参与偏头痛发作。     

Adrenomedullin and ocular inflammation in the rabbit

Adrenomedullin administered peripherally in the rabbit (at doses of 1.25, 2.5 and 5 microg/kg ) caused a dose-dependent conjunctival hyperemia accompanied by an increase of inflammatory cell number and prostaglandin E(2) concentration in the aqueous humor, and of uveal vascular response and myeloperoxidase activity. The inflammatory effect of the peptide, injected at the dose of 5 microg/kg, was abolished by pretreatment with the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methylester (50 mg/kg, i.v.). Moreover, the i.v. pretreatment with the calcitonin gene-related peptide 8-37 fragment (calcitonin gene-related peptide, CGRP-(8-37), 2.5 microg/kg), receptor antagonist of CGRP, did not inhibit the conjunctival hyperemia. In contrast, the i.v. pretreatment with the adrenomedullin receptor antagonist, adrenomedullin-(22-52) fragment (2.5 microg/kg), abolished adrenomedullin-induced ocular inflammation. These results suggest that adrenomedullin causes conjunctival hyperemia, and this effect involves the nitric oxide system acting through specific adrenomedullin receptors.     

Nitric oxide influences the release of histamine and glutamate in the rat hypothalamus

To investigate the influence of nitric oxide (NO) on the release of histamine and glutamate, the anterior hypothalamus of anaesthetized rats was superfused through a push-pull cannula either with artificial cerebrospinal fluid (CSF) or with various drugs dissolved in CSF.Hypothalamic superfusion with the NO-donating compounds linsidomine (200 mol/l) or diethylamine-NO (DEANO, 100 mol/l) led to a pronounced and sustained decrease in the histamine release rate, whereas the release rate of glutamate was enhanced. Superfusion with the inhibitor of NO synthase L-N^G-nitro-L-arginine methyl ester (L-NAME, 200 mol/l) increased the histamine release rate. The inhibitory effect of 200 mol/l linsidomine was abolished by atropine (10 mol/l). Superfusion with the glutamate receptor agonists glutamate (100 mol/l) or N-methyl-D-aspartate (NMDA, 50 mol/l) enhanced the histamine release rate. In the presence of linsidomine, the releasing effect of NMDA was not changed.These findings demonstrate that the release of histamine in the hypothalamus is diminished by endogenous NO. This effect of NO on histamine release seems to be due to enhanced release of acetylcholine from vicinal cholinergic neurons via stimulation of muscarinic acetylcholine receptors located presynaptically on histaminergic neurons. The NO-induced glutamate release seems to exert a subordinate stimulatory effect on histamine release. Finally, the inhibition of histamine release by NO is not due to blockade of NMDA receptors.This work was supported by the Jubiläumsfonds der österreichischer Nationalbank     

Propofol ameliorates liver dysfunction and inhibits aortic superoxide level in conscious rats with endotoxic shock

Propofol, widely used as a sedative agent, is known to exert antioxidant and anti-inflammatory effects in vitro. We studied the effects of propofol on hemodynamics and the function of several organs in conscious rats with endotoxemia. Intravenous injection of rats with endotoxin (lipopolysaccharide) caused hypotension, vascular hyporeactivity and tachycardia as well as significant lung, liver and kidney damage. Hepatocellular damage caused by lipopolysaccharide for 6 h was significantly attenuated in the lipopolysaccharide+propofol group. Aortic superoxide anion (O(2)(radical)(-)) production, but not plasma nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) level, was also suppressed by propofol in lipopolysaccharide-injected rats. Light microscopy showed that propofol attenuated the marked infiltration of neutrophils in liver tissues from lipopolysaccharide-injected rats. Moreover, the survival rate of the lipopolysaccharide+propofol group at 16 h was significantly increased when compared with that of the lipopolysaccharide group (53% vs. 12%). These results suggest that inhibition of aortic O(2)(radical)(-) production and amelioration of liver dysfunction contribute to the beneficial effect of propofol in conscious rats with endotoxic shock.     

Lipoxin A4 inhibits cholinergic neurotransmission through nitric oxide generation in the rabbit trachea

The effect of lipoxin A₄ and lipoxin B₄ on cholinergic neurotransmission in rabbit tracheal segments was studied under isometric conditions in vitro. Lipoxin A₄ attenuated the contractile responses to electrical field stimulation and caused a rightward shift of the frequency-response curves, so that the stimulus frequency required to produce a half-maximal effect (ES₅₀) increased from 8.1 ± 0.8 to 25.7 ± 1.9 Hz (P < 0.001), whereas lipoxin B₄ had no effect. In contrast, lipoxin A₄ did not alte contractile responses to acetylcholine. Pretreatment of tissues with N^G-nitro- -arginine methylester inhibited the effect of lipoxin A₄ on electrical field stimulation, but N^G-nitro- -arginine methylester did not. This inhibition by N^G-nitro- -arginine methylester was reversed by -arginine but not by -arginine. These results suggest that lipoxin A₄ prejunctionally reduces the vagal nerve-mediated contraction of airway smooth muscle, probably by inhibiting the release of acetylcholine, and that this effect may be exerted through stimulation of nitric oxide generation.     

Stimulatory effects of nitric oxide donors on gastric acid secretion in isolated mouse stomach

We previously reported on the stimulatory role of endogenous nitric oxide (NO) in gastric acid secretion. In the present study, we investigated the effects of NO donors on acid secretion in isolated mouse stomach. Nitroprusside (100 μM–1 mM) inhibited the gastric acid secretion induced by histamine (500 μM) in a concentration-dependent manner. In addition, nitroprusside abolished the acid secretion induced by bethanechol (100 μM) and by electrical stimulation (10 Hz) of the vagus nerve. On the other hand, nitroprusside, 75 μM, which did not affect the acid secretion induced by histamine, itself elicited an increase in acid secretion. The acid secretion induced by 75 μM nitroprusside was inhibited by 10 μM famotidine, a histamine H₂ receptor antagonist. These results suggest that NO donors at high doses act on gastric parietal cells, resulting in inhibition of the stimulated acid secretion, and, at lower doses, facilitate histamine release from histamine-containing cells, leading to the increased acid secretion.     

冠心病患者血一氧化氮/一氧化氮酶和内皮素检测的临床意义

目的　探讨了 NO/ NOS和 ET在冠心病患者中的变化。方法　分别应用生化法和放免法检测了3 9例冠心病患者血 NO/ NOS和 ET含量 ,并与 3 5名正常健康人作对照。结果　冠心病患者血 NO水平低于正常人 ( P<0 .0 5 ) ,NOS和 ET水平高于正常人 ( P<0 .0 1)。结论　 NO/ NOS和 ET水平的变化与冠心病的发生与发展密切相关     

Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-kappa B and c-Jun NH2-terminal kinase

Triptolide (PG490) is a natural, biologically active compound extracted from the Chinese herb Tripterygium wilfordii. It has been shown to possess potent anti-inflammatory and immunosuppressive properties. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, triptolide inhibits nitric oxide (NO) production in a dose-dependent manner and abrogates inducible nitric oxide synthase (iNOS) gene expression. To investigate the mechanism by which triptolide inhibits murine iNOS gene expression, we examined activation of mitogen-activated protein kinases (MAP kinases) and nuclear factor-kappa B (NF-kappa B) in these cells. Addition of triptolide inhibited phosphorylation of c-Jun NH(2)-terminal kinase (JNK) but not that of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein kinase. In addition, triptolide significantly inhibited the DNA binding activity of NF-kappa B. Taken together, these results suggest that triptolide acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of NF-kappa B and JNK activation.     

Role of nitric oxide in allergic inflammation and bronchial hyperresponsiveness

The role of nitric oxide (NO) in allergic inflammation and bronchial hyperresponsiveness is unclear. We studied a selective prodrug nitric oxide synthase (NOS)-2 inhibitor, L-N(6)-(1-iminoethyl)lysine 5-tetrazole amide (SC-51). In ovalbumin-sensitized and challenged rats, exhaled NO levels increased by 3 h following challenge (3.73 +/- 0.74 ppb; P < 0.05), peaking at 9 h (11.0 +/- 2.75; P < 0.01) compared to saline controls (1.87 +/- 0.26; P < 0.05 and 2.81 +/- 0.18; P < 0.01). Immunoreactive lung NOS2 expression was increased in ovalbumin-challenged rats compared with ovalbumin-sensitized, saline-challenged rats at 8 h post-challenge. SC-51 (10 mg/kg; p.o.) inhibited allergen-induced increase in exhaled NO levels to 1.3 +/- 0.17 ppb. SC-51 inhibited bronchial hyperresponsiveness in ovalbumin-sensitized and challenged rats (P < 0.05). In sensitized non-exposed rats, SC-51 increased bronchial responsiveness (P < 0.05). SC-51 reduced the allergen-induced increase in bronchoalveolar lavage neutrophils, but caused a nonsignificant reduction in bronchial mucosal eosinophil numbers. NO generated through NOS2 contributes to allergen-induced bronchial hyperresponsiveness but not to bronchial eosinophilia, indicating that these are independently expressed.     

一氧化氮对急性胰腺炎影响的研究进展

急性胰腺炎(Acute pancreatitis,AP)是一种病情凶险,病死率高的临床常见急腹症。AP的发病机制是一个复杂的、多种因素参与的病理生理过程,目前明确的发病机制尚未完全阐明。近年来,大量研究表明一氧化氮(Nitric oxide,NO)在急性胰腺炎的发生发展中起重要的作用。本文就NO对AP的影响作一综述。     

血必净对急性胰腺炎大鼠血清一氧化氮的影响

目的探讨急性胰腺炎(Acute pancreatitis,AP)大鼠血清一氧化氮(Nitric oxide,NO)的变化及血必净注射液对其的影响。方法将90只SD大鼠随机分为假手术组、急性胰腺炎组、血必净组,各组再分为3、6、12 h亚组,假手术组开腹后仅行简单的胰腺翻动,急性胰腺炎组开腹后经十二指肠乳头逆行胆胰管注射5%牛黄胆酸钠建立AP模型,血必净组在AP组基础上予血必净注射液治疗,分别在各时间点采血观察血清中淀粉酶(AMY)、一氧化氮(NO)的变化,并进行胰腺组织病理学检查。结果与假手术组相比,AP组中AMY、NO浓度明显增高,差异有统计学意义(P<0.05);与AP组相比,血必净组中AMY、NO浓度明显降低,差异有统计学意义(P<0.05),光镜下AP组胰腺组织损伤明显,而血必净组损伤明显改善。结论 NO参与急性胰腺炎的发生发展过程,血必净注射液能显著降低血清NO,减轻胰腺组织的损伤。     

Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation

Nitric oxide (NO) has been shown to act as a mediator of cytokines in bone tissue. We have previously demonstrated that vanadium compounds are insulin- and growth factor-mimetic compounds in osteoblasts in culture, although high doses are toxic to these cells. In this study, we measured NO production in two osteoblast-like cells (UMR106 and MC3T3E1) incubated with different concentrations (2.5–100 μM) of vanadate. Vanadate induced NO release in a biphasic manner, with levels being significantly increased at concentrations over 50 μM. The NO donor, sodium nitroprusside, mimicked the vanadate effect: it inhibited cell growth and alkaline phosphatase activity in a dose-dependent manner. Vanadate enhanced the NO synthases, the endothelial and inducible (eNOS and iNOS) isoforms, in a dose-dependent manner. Experiments performed with the ionophore A23187 and EGTA suggested that vanadate-induced NO production involves Ca²⁺-dependent and -independent mechanisms. Altogether, our results suggest that NO may play a critical role in the bioactivity of vanadium in osteoblast-like cells.     

Attenuation of morphine tolerance and dependence by aminoguanidine in mice

The effect of aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, on morphine-induced tolerance and dependence in mice was investigated in this study. Acute administration of aminoguanidine (20 mg/kg, p.o.) did not affect the antinociceptive effect of morphine (10 mg/kg, s.c.) as measured by the hot plate test. Repeated administration of aminoguanidine along with morphine attenuated the development of tolerance to the antinociceptive effect of morphine. Also, the development of morphine dependence as assessed by naloxone-precipitated withdrawal manifestations was reduced by co-administration of aminoguanidine. The effect of aminoguanidine on naloxone-precipitated withdrawal was enhanced by concurrent administration of the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, dizocilpine (0.25 mg/kg, i.p.) or the non-specific nitric oxide synthase (NOS) inhibitor, l-N(G)-nitroarginine methyl ester (l-NAME; 5 mg/kg, i.p.) and antagonized by concurrent administration of the nitric oxide (NO) precursor, l-arginine (50 mg/kg, p.o.). Concomitantly, the progressive increase in NO production, but not in brain glutamate level, induced by morphine was inhibited by repeated administration of aminoguanidine along with morphine. Similarly, co-administration of aminoguanidine inhibited naloxone-induced NO overproduction, but it did not inhibit naloxone-induced elevation of brain glutamate level in morphine-dependent mice. The effect of aminoguanidine on naloxone-induced NO overproduction was potentiated by concurrent administration of dizocilpine or l-NAME and antagonized by concurrent administration of l-arginine. These results provide evidence that blockade of NO overproduction, the consequence of NMDA receptor activation, by aminoguanidine, via inhibition of iNOS, can attenuate the development of morphine tolerance and dependence.     

Inhibitory effect of N-nitro-

目的：探讨肝硬化患者血NO、TNF、ET与EPS的关系。方法：分别应用酶法和放射免疫分析法测定了84例肝硬化患者血NO、NOS、ET和EPS含量，并与35名正常健康人作对照。结果：肝硬化患者血NO、TNF、EPS含量高于正常人组（P＜0．05－0．01），ET水平低于正常人组（P＜0．01－0．01），且与内毒素含量的高低密切相关。结论：肝硬化患者血NO、TNF、ET水平的高低其内毒素为主要诱因。     

肝硬化患者一氧化氮、一氧化氮酶、肿瘤坏死因子、内皮素、内毒素水平的相关性研究

目的：探讨肝硬化患者血NO、TNF、ET与EPS的关系。方法：分别应用酶法和放射免疫分析法测定了84例肝硬化患者血NO、NOS、ET和EPS含量，并与35名正常健康人作对照。结果：肝硬化患者血NO、TNF、EPS含量高于正常人组（P＜0．05－0．01），ET水平低于正常人组（P＜0．01－0．01），且与内毒素含量的高低密切相关。结论：肝硬化患者血NO、TNF、ET水平的高低其内毒素为主要诱因。     

Interleukin-1 inhibits angiotensin II-stimulated protein kinase B pathway in renal mesangial cells via the inducible nitric oxide synthase

Exposure of rat renal mesangial cells to angiotensin II and angiotensin III leads to a rapid phosphorylation and activation of the protein kinase B (PKB) pathway. The angiotensin II analogs angiotensin-(1-7), angiotensin-(1-6) and angiotensin-(3-8) were unable to activate PKB. The angiotensin II and III effects are mediated by the angiotensin type 1 receptor as documented by the inhibitory action of valsartan. Furthermore, angiotensin II-induced activation of PKB involves neither a pertussis toxin-sensitive pathway nor the small G proteins of the Rho/Rac/cdc42 family, but is completely blocked by inhibitors of the PI 3-kinase. Moreover, angiotensin II-stimulated PKB activation is inhibited by long-term pretreatment with interleukin-1 beta, an effect that is reversed by the NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA). Similarly, the nitric oxide donor (Z)-1-[2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (Deta-NO) blocks the angiotensin II-induced PKB activation. The NO-mediated inhibition of PKB activation in turn is reversed by the phosphatase inhibitor calyculin A but not by ocadaic acid, implying the induction of a protein phosphatase 1 activity by NO.     

人参皂苷对内皮细胞ECV304代谢NO的影响

OBJECTIVEto study the mechanism of Ginsenosides preventive and remedial effect on cardio-vascular diseases. METHODThe effect of Ginsenosides on the nitric oxide(NO) Production in normal ECV304 and oxidation injury ECV304 was studied with Serum Pharmacol     

支气管肺炎患儿血浆一氧化碳和内皮素水平检测的临床意义

目的　探讨一氧化氮 (NO)和内皮素 (ET)在支气管肺炎患儿血浆中的含量变化。方法　应用生化法和放免法测定 38例患儿血浆 NO和 ET含量 ,并以 35名正常健康儿童作对照。结果　支气管肺炎急性期患儿血浆 NO和 ET水平非常显著地高于对照组 (P<0 .0 1) ,至恢复期与对照组比较 ,则差异无显著性 (P>0 .0 5 )。结论　NO和 ET参与了支气管肺炎的发生和发展过程 ,动态检测有一定的临床价值     

Nitric oxide supports atrial function in sepsis: relevance to side effects of inhibitors in shock

The mechanisms underlying myocardial dysfunction in sepsis remain poorly understood. The theoretical benefits of nitric oxide synthase (NOS) inhibition in reversing the haemodynamic changes that characterise septic shock have not been supported by clinical trials, some of which have demonstrated detrimental myocardial effects. We have therefore assessed the effects of endotoxaemia on NOS enzyme expression as well as a number of functional responses of myocardial tissue from rats. Atrial tissue expressed high levels of mRNA for inducible (i) NOS and released increased levels of nitrite after animals were treated with endotoxin. In parallel, the inotropic response stimulated by isoprenaline was reduced in atria from endotoxin-treated animals, an effect that was reversed when endogenous release of NO was maximised. Our results suggest that myocardial contractility is maintained by NO production and that inhibitors may compromise cardiac output; this may explain the deleterious effects of NOS inhibition on cardiac function in clinical trials.