血浆一氧化氮在小儿充血性心力衰竭时的变化及意义

目的 探讨小儿充血性心力衰竭(CHF)时血浆一氧化氮(NO)的变化及意义。方法 测定先天性心脏病合并CHF组17例与健康小儿作对照组15例、支气管肺炎(支肺炎)合并CHF组16例与支气管肺炎组15例及支肺炎合并CHF纠正前后的血浆NO水平。结果 先天性心脏病合并CHF组的血浆水平高于对照组且差异有非常显著意义(P＜0．001)，支肺炎合并CHF组(CHF纠正前)的血浆NO水平高于支肺炎组且差异有非常显著意义(P＜0．001)。结论 CHF患儿的血浆NO水平升高是CHF患儿的病理生理特征之一，N0参与CHF的病理生理，可作为判断CHF的一个辅助指标。     

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.     

Helicobacter pylori lipopolysaccharide-provoked injury to rat gastroduodenal microvasculature involves inducible nitric oxide synthase

The actions of a purified Helicobacter pylori lipopolysaccharide (3 mg kg⁻¹, i.v.) on rat gastric antral and duodenal microvascular integrity (determined as radiolabelled albumin leakage) and the expression of the inducible nitric oxide (NO) synthase (iNOS; assessed by the citrulline assay) were investigated 4 h after challenge. Significant increases of albumin leakage and expression of iNOS in both antral and duodenal tissues were observed following challenge. Concurrent administration of the selective iNOS inhibitor, 1400W (N-(8-(aminomethyl)benzyl)-acetamidine; 0.2–1 mg kg⁻¹, s.c.), with lipopolysaccharide, caused a dose-dependent attenuation of the gastric and duodenal albumin leakage. Thus, H. pylori lipopolysaccharide can initiate the expression of iNOS in the stomach and duodenum following systemic challenge, which can provoke gastroduodenal microvascular dysfunction.     

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。     

Balloon angioplasty and induction of non-endothelial nitric oxide synthase in rabbit carotid arteries

The purpose of the study was to evaluate whether balloon angioplasty is associated with changes in nitric oxide synthase (NO synthase) activity. Normal rabbit carotid arteries were examined 10 min or 1, 2, 3 or 10 weeks after angioplasty with 2 or 2.5-mm balloons. Immunohistology was used to evaluate intimal thickening and endothelial cell regeneration. The NO synthase activity was studied functionally using isolated segments in organ chambers. Immunohistochemistry of the endothelial cell markers von Willebrand factor and platelet endothelial cell adhesion molecule-1 indicated that the regeneration of endothelial cells from patchy islands that remained after angioplasty was virtually complete within 2 weeks. However, the endothelium-dependent relaxations elicited by acetylcholine remained impaired up to 10 weeks after dilatation. Contractions elicited by 5-hydroxytryptamine (5-HT) were attenuated, but were significantly augmented by the NO synthase blocker, nitro- -arginine. Furthermore, in contrast to normal arteries, the balloon-treated arteries developed marked contractions in response to nitro- -arginine methyl ester ( -NAME), contractions which could be reversed by -arginine. The latter contractions and relaxations were not influenced by endothelial removal. These results suggest that although the endothelium quickly regenerates after severe balloon injury, the endothelium-dependent release of nitric oxide remains disturbed. However, the functional data also suggest that angioplasty led to a significant induction of NO synthase in ‘non-endothelial’ cells of the artery.     

热毒清对内毒素性发热家兔体温及血浆NO的影响

目的观察热毒清对内毒素性发热家兔的体温以及血浆NO水平的影响,并比较不同剂量的药效。方法采用内毒素注射的方法制成发热家兔模型60只,随机分为6组,阿司匹林组(A组),热毒清高剂量组(B组),热毒清中剂量组(C组),热毒清低剂量组(D组),双黄连口服液组(E组),对照组(F组),每组10只,观察比较各组体温变化。结果与对照组比较,热毒清中剂量组及热毒清高剂量组对发热家兔的体温有明显的降温作用,且比阿司匹林组作用持续时间延长;热毒清低剂量组及双黄连组对发热家兔的体温无明显的降温作用。结论热毒清高剂量及热毒清中剂量能够降低内毒素性发热家兔的体温,改善症状和体征,降低血浆NO水平。作用机理可能是调控细胞因子网络,抑制循环血中NO的产生。     

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。     

血浆一氧化氮、一氧化氮合酶和基质金属蛋白酶9在子宫颈癌中的临床意义

目的 探讨血浆一氧化氮（NO）、一氧化氮合酶（NOS）和基质金属蛋白酶（MMP-9）水平在子宫颈癌中的变化及临床意义.方法 经病理活检确诊为宫颈癌患者69例,分别于手术前1d、术后15 d、30 d空腹抽取外周静脉血,健康对照组取空腹静脉血,采用化学比色法和ELISA法分别测定血浆中NO、NOS和MMP-9含量,比较上述指标的变化及相关性.结果 宫颈癌患者血浆中NO、NOS、MMP-9的水平与健康对照组相比明显增高.宫颈癌患者手术前与手术后15 d、30 d NO水平比较,手术后NO、NOS、MMP-9的水平均明显降低,但仍明显高于对照组.宫颈癌患者有淋巴结转移者NO、NOS、MMP-9水平明显高于无淋巴结转移者;相关性分析表明,血清中MMP-9与NO、NOS呈明显正相关性.结论 检测血浆中NO、NOS和MMP-9水平的变化,对宫颈癌的病情判断及临床治疗指导具有参考意义.     

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.     

The inhibition of inducible nitric oxide synthase and oxidative stress by agmatine attenuates vascular dysfunction in rat acute endotoxemic model

Vascular dysfunction leading to hypotension is a major complication in patients with septic shock. Inducible nitric oxide synthase (iNOS) together with oxidative stress play an important role in development of vascular dysfunction in sepsis. Searching for an endogenous, safe and yet effective remedy was the chief goal for this study. The current study investigated the effect of agmatine (AGM), an endogenous metabolite of l-arginine, on sepsis-induced vascular dysfunction induced by lipopolysaccharides (LPS) in rats. AGM pretreatment (10 mg/kg, i.v.) 1 h before LPS (5 mg/kg, i.v.) prevented the LPS-induced mortality and elevations in serum creatine kinase-MB isoenzyme (CK-MB) activity, lactate dehydrogenase (LDH) activity, C-reactive protein (CRP) level and total nitrite/nitrate (NOx) level after 24 h from LPS injection. The elevation in aortic lipid peroxidation illustrated by increased malondialdehyde (MDA) content and the decrease in aortic glutathione (GSH) and superoxide dismutase (SOD) were also ameliorated by AGM. Additionally, AGM prevented LPS-induced elevation in mRNA expression of iNOS, while endothelial NOS (eNOS) mRNA was not affected. Furthermore AGM prevented the impaired aortic contraction to KCl and phenylephrine (PE) and endothelium-dependent relaxation to acetylcholine (ACh) without affecting endothelium-independent relaxation to sodium nitroprusside (SNP). In conclusion: AGM may represent a potential endogenous therapeutic candidate for sepsis-induced vascular dysfunction through its inhibiting effect on iNOS expression and oxidative stress.     

支气管哮喘患儿血内皮素-1和一氧化氮水平测定及临床意义

目的　探讨内皮素 1(Endothelia 1,ET 1)和—氧化氮 (nitrcoxide ,NO )在儿童哮喘发病机制中的作用。方法　对 40例支气管哮喘患儿和 40例正常儿童进行了血浆ET 1及血清NO水平检测。结果　哮喘急性期患儿血ET 1和NO明显高于缓解期 (P <0 0 1) ,缓解期ET 1和NO虽有所下降 ,但仍高于对照组(P <0 0 5)。结论　ET 1和NO水平与哮喘病情严重程度成正相关 ,是反映哮喘严重程度的良好指标     

Physiological release of nitric oxide is dependent on the level of vascular tone

The presser effect of N^G-methyl-L-arginine (NMA) was tested in urethane-anesthetized rats which were untreated (control) or devoid of sympathetic tone. In contrast with controls, the NMA response was attenuated by pithing or ganglionic blockade. In pithed rats, the induction of moderate or intense vasoconstriction with constant phenylephrine infusion restored or augmented, respectively, the NMA pressor response. Our data suggest that vascular tone may physiologically regulate the release of nitric oxide in vivo.     

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     

Modulation of neuroeffector transmission by endogenous nitric oxide: a role for acetylcholine receptor-activated nitric oxide formation, as indicated by measurements of nitric oxide/ nitrite release

Nitric oxide (NO) synthase inhibitors enhanced nerve-mediated contractile responses in guinea pig ileum longitudinal muscle, likely via a prejunctional effect on substance P-like neuroeffector transmission. Supporting a modulatory role for NO, application of NO through administration of acid sodium nitrite evoked marked inhibitory effects on responses to transmural nerve stimulation. Substance P-like responses to nerve stimulation were abolished by substance P receptor antagonists and were enhanced by atropine, indicating a cholinergic influence on substance P-like neuroeffector transmission. Since acetylcholine can evoke release of NO from endothelium, the possible role of acetylcholine in NO release in ileum was examined. The release of NO/nitrite, determined by chemiluminescence, was inhibited by N^G-monomethyl-L-arginine (L-NMMA), by calcium removal, by tetrodotoxin or by atropine, indicating a nerve-mediated control of NO production. A basis for the NO release is likely to be spontaneous neuronal activity, where release of acetylcholine, with subsequent muscarinic receptor activation, contributes to stimulation of NO formation.     

一氧化氮及一氧化氮合酶在成年与老年大鼠前列腺中的变化

目的:研究一氧化氮(NO)及一氧化氮合酶(NOS)在成年与老年大鼠前列腺中的变化,探讨在大鼠前列腺老年化过程中的临床意义。方法:取4月龄及20月龄SD雄性大鼠各6只,分别取前列腺组织匀浆,检测其NO与NOS活性。结果:老年组大鼠的NO与NOS活性明显低于成年组(P<0.05)。结论:老年大鼠前列腺组织中NO水平及NOS活性的降低可能与前列腺良性增生及功能减退有关。     

Quinacrine increases endothelial nitric oxide release: role of superoxide anion

The effect of acute quinacrine treatment on agonist-induced nitric oxide (NO) release was investigated in cultured human endothelial cells using electrochemical monitoring of the in situ NO concentration. Quinacrine dose-dependently increased NO release with an apparent EC50 of 0.2 microM and a maximal effect at 1 microM. Quinacrine did not modify the dependence of NO release on extracellular L-arginine. Acceleration or deceleration of O2- dismutation, which altered NO release in control cells, did not modify it in quinacrine-treated cells. Quinacrine did not modify NO amperometric signal or reaction with O2- produced by xanthine oxidation. In the presence of quinacrine, agonist-induced NO release became Mg2+ -independent and could not be attributed to an inhibition of phospholipase A2 activity. Quinacrine made NO release insensitive to Cu2+ chelation. The present study demonstrates that acute treatment by low quinacrine concentrations increases endothelial NO release, possibly through an inhibition of O2- production.     

Inducible nitric oxide synthase is involved in corticotropin-releasing hormone-mediated central sympatho-adrenal outflow in rats

Brain nitric oxide (NO), recognized as a neurotransmitter or a neuromodulator, is mainly generated either by neuronal NO synthase (NOS) or by inducible NOS. NO has been shown to activate cyclooxygenase (a prostaglandin-forming enzyme) in addition to guanylate cyclase. Recently, we reported that the intracerebroventricularly (i.c.v.) administered corticotropin-releasing hormone (CRH) increases plasma catecholamines through brain cyclooxygenase-dependent mechanisms in rats. In the present experiments, therefore, we examined whether NO is involved in the CRH-induced increase of plasma catecholamines using urethane-anesthetized rats. I.c.v. administered CRH increased plasma noradrenaline and adrenaline in a dose-dependent manner (0.5, 1.5, and 3.0 nmol/animal). The CRH (1.5 nmol/animal, i.c.v.)-induced increase of plasma catecholamines was reduced by N(omega)-nitro-L-arginine methyl ester (a non-selective inhibitor of NOS) [111 nmol (30 microg)/animal, i.c.v.], but not by the same dose of N(omega)-nitro-D-arginine methyl ester (an inactive isomer of N(omega)-nitro-L-arginine methyl ester). The CRH-induced increase of plasma catecholamines was also reduced either by cycloheximide (an inhibitor of protein synthesis) [107 nmol (30 microg)/animal, i.c.v.] or by S-methylisothiourea (an inhibitor of inducible NOS) [71 nmol (20 microg) and 711 nmol (200 microg)/animal, i.c.v.]. These results suggest the involvement of brain inducible NOS in the CRH-induced activation of the central sympatho-adrenomedullary outflow in rats.     

一氧化氮合酶在实验性急性胰腺炎胰腺组织中基因表达的研究

目的：探讨急性胰腺炎（AP）发病机制中与一氧化氮（NO）的关系。方法：采用实验性急性胰腺炎的动物模型，对AP形成后不同时相的胰腺组织中一氧化氮合酶（cNOS）的基因表达进行了检测。同时检测了血清淀粉酶、红细胞超氧化物歧化酶（SOD）和病理组织。结果：术后24小时已形成出血性、坏死性AP，胰腺组织cNOSmRNA在术后36小时达高峰，随着时间的延长，cNOSmRNA进一步下降。结论：在AP初期，NO主要由cNOS产生，以保证为主，以后cNOS下降，可导致AP发生不可逆损害，临床可通过寻找特异性诱cNOS试剂，为临床治疗AP开辟新的领域。     

Brain inducible nitric oxide synthase is involved in interleukin-1beta-induced activation of the central sympathetic outflow in rats

Nitric oxide (NO) has been recognized as a neurotransmitter or a neuromodulator in the central nervous system. Brain NO is mainly generated either by neuronal NO synthase (NOS) or by inducible NOS. Previously we reported that central NO is involved in the elevation of plasma noradrenaline levels induced by intracerebroventricularly (i.c.v.) administered interleukin-1beta in rats [Eur. J. Phamacol. 317 (1996) 61]. In the present study, therefore, we tried to characterize which type of NOS isoforms is involved in the cytokine-induced responses using selective inhibitors of each NOS isoform in urethane-anesthetized rats. I.c.v. administered interleukin-1beta (100 ng/animal) elevated plasma levels of noradrenaline but not adrenaline. The cytokine-induced elevation of plasma noradrenaline levels was attenuated by cycloheximide, an inhibitor of protein synthesis, in a dose-dependent manner (10 and 20 microg/animal, i.c.v.). S-ethylisothiourea (0.1 and 0.5 microg/animal, i.c.v.), an inhibitor of inducible NOS, dose-dependently reduced the cytokine-induced elevation of plasma noradrenaline levels, while 7-nitroindazole (5 and 10 microg/animal, i.c.v.), an inhibitor of neuronal NOS, had no effect. These results suggest the involvement of brain inducible NOS in the interleukin-1beta-induced activation of the central sympathetic outflow in rats.