Reversible and irreversible airway inflammation and fibrosis in mice exposed to inhaled ovalbumin

Objective and design: We examined the reversibility of several changes in the lungs and airways of mice immediately after exposure to ovalbumin aerosol and after a period of recovery breathing clean air.Methods: Mice were exposed for 1, 2, 4, 6, 8, or 10 weeks, with recovery in clean air for 1–3 weeks.Results: Airway collagen content, exhaled NO, airway mucous cell hyperplasia, and lung lavage inflammatory cell content increased upon exposure to ovalbumin aerosol. All parameters except airway fibrosis decreased partially or completely to control values with recovery in clean air.Conclusions: Airway mucous cell hypertrophy and hyperplasia appear to be completely reversible after recovery in clean air, while exhaled NO and airway inflammation appear to be mostly reversible, except for persistence of lymphocytes in the lung lavage fluid. Airway fibrosis appears to be reversible when mice are exposed to ovalbumin aerosol for periods of up to 4 weeks of exposure, but becomes irreversible after 6 or more weeks of exposure.Received 30 June 2004; returned for revision 24 September 2004; accepted by J. S. Skotnicki 13 October 2004     

躁狂症患者血清一氧化氮水平研究

目的：了解躁狂症患者的血清一氧化氮(NO)水平。方法：对20例躁狂症患者的血清NO水平进行检测，采用Bech-Rafaelsen躁狂量表(BRMS)进行评定。以18例正常体检者为对照。结果：躁狂症组的血清NO水平明显高于正常对照组，血清NO水平与BRMS分之间未发现有相关性。结论：躁狂症患者存在相对较高的血清NO水平，可能是躁狂发作的病理生理基础。     

一氧化氮与卵巢生理

NO是一种结构简单的气体,是脊椎动物体内已发现的分子量最小的生物活性分子。NO作为一种信使分子,生物作用广泛,在生殖系统发挥重要作用。本文着重介绍NO作为卵巢内重要的调节因子,在调节卵泡发育、卵母细胞成熟、排卵、黄体的形成与退化、激素合成等方面的研究进展。     

高血压病血管内皮功能障碍及治疗

内皮细胞功能障碍是近年来的热门研究课题,从基础到临床受到广泛重视。高血压是发病率最高的心血管疾病,其发病环节与内皮细胞功能关系密切,二者均是心脑血管事件链中的重要环节。本文回顾了多种内皮因子的功能及其与高血压的关系,高血压病内皮功能障碍的可能机制,肱动脉超声检查方法以及内皮功能障碍的治疗对策。     

大鼠上丘一氧化氮合酶阳性神经元的发育

目的：研究大鼠胚胎时期及生后早期一氧化氮合酶(NOS)阳性神经元在上丘的分布，进一步探讨一氧化氮(NO)在上丘发育过程中的作用。方法：应用还原型尼克酰胺腺嘌呤二核苷酸脱氢酶(NADPH—d)组织化学方法观察孕17d起至生后14d大鼠上丘NOS阳性神经元的发育。结果：孕20d上丘深白层与深灰层出现NOS阳性神经元。P0上丘中层也观察到NOS阳性神经元。随着发育，阳性神经元增多，胞体增大，染色加深。到P14，视神经层出现少许：NOS阳性神经元，浅灰层观察到大量的NOS阳性神经元。结论：胚胎20天上丘深层首先出现NOS阳性神经元并沿腹背方向发生，提示NO在上丘发育过程中起着重要作用。     

Induction of NADPH-diaphorase activity in the hippocampus in a rat model of cerebral ischemia and ischemic tolerance

Preconditioning of the brain with sublethal ischemia induces tolerance to subsequent lethal periods of ischemia (ischemic tolerance). In this study, we used NADPH-diaphorase histochemistry to investigate the postischemic changes of nitric oxide synthase (NOS) in the hippocampus in a rat model of cerebral ischemia and ischemic tolerance. Forebrain ischemia was induced by 4-vessel occlusion for 3 min as an ischemic preconditioning. Three days after the preconditioning or sham operation, second ischemia was induced for 6 min. A transient increase in NADPH-diaphorase activity, beginning after 2 h and maximal after 1 day, was observed in CA1 pyramidal neurons of rats subjected to 3 min of preconditioning ischemia as well as 6 min of subsequent ischemia both with and without preconditioning. In addition, expression of NADPH-diaphorase activity was seen in reactive glial cells in the damaged CA1 region of animals subjected to 6 min of ischemia without preconditioning. Thus, direct involvement of increased NADPH-diaphorase activity in ischemic tolerance was not suggested because the increased NADPH-diaphorase activity preceded the induction of ischemic tolerance which takes place 1–7 days after preconditioning. However, the present findings suggest that the induction of neuronal NADPH-diaphorase activity occurs in response to cerebral ischemia.     

Antiepileptic effects of inhibitors of nitric oxide synthase examined in pentylenetetrazol-induced seizures in rats

The effects of intraperitoneal and methyl ester, specific inhibitors of nitric oxide (NO) synthase, were examined on the pentylenetetrazol (PTZ)-induced seizures in rats. The incidence and latency for the onset of myoclonic jerks, clonic seizures, and tonic generalized extension were observed as specific parameters among PTZ-induced seizures. Both drugs preferentially suppressed the tonic generalized extension and prolonged the latency for the onset of each parameter, suggesting NO has a significant effect on the PTZ-induced seizure.     

The effect of endothelium-derived nitric oxide on ex vivo whole blood platelet aggregation in man

Summary The effects of changes in endogenous endothelium-derived nitric oxide (NO) on forearm blood flow and ex vivo platelet aggregation have been studied in 7 healthy volunteers.Measurements were made of forearm blood flow and ex vivo collagen-stimulated platelet aggregation during unilateral brachial artery infusions of saline, acetylcholine (ACh), N^G monomethyl-L-arginine (L-NMMA), and prostacyclin (PGI₂). The uninfused arm acted as a control.Forearm blood flow was increased by ACh, an agent which stimulates NO release, and decreased by L-NMMA, an agent which stereospecifically inhibits NO synthesis.Collagen-stimulated platelet aggregation measured ex vivo in whole blood draining the infused arm was unaltered by either ACh or L-NMMA. Conversely, PGI₂, an agent which acts independently of NO, caused an increase in forearm blood flow which was accompanied by significant inhibition of platelet aggregation.The results suggest that release of endothelium-derived NO in quantities sufficient to cause substantial changes in blood vessel tone does not lead to changes in platelet aggregation in the blood flowing through the vessels. It is, however, still possible that endothelium-derived NO modulates platelet activity at the level of the endothelium. Present address: Department of Medicine and Therapeutics, University of Aberdeen Polwarth Building, Forrester Hill, Aberdeen, UK     

低剂量混配农药对家兔血浆谷胱甘肽过氧化物酶和一氧化氮的影响

目的 探讨低剂量混配农药对家兔脂质过氧化及一氧化氮（NO）浓度的影响及意义。方法 将家兔随机分为6个混配农药染毒组、1个丙溴磷染毒组和1个对照组，于不同的时间测定各组血清胆碱酯酶（ChE)活力、谷胱甘肽过氧化物酶（GSH-Px)活力及一氧化氮（NO）浓度。结果 除较高剂量混配农药组外，其余各组染毒后的ChE活力均大于对照组实验前平均值的70%。随着染毒时间的延长农药混配组血浆GSH-Px活力高于或显著高于同时间的单剂量组和对照组，而血浆NO的浓度则呈降低趋势。结论 低剂量含有机磷的混配农药在导致ChE活力降低之前即可造成脂质过氧化增强和NO浓度的降低。     

Neurotransmitter release evoked by α-latrotoxin in the smooth muscle of the female pig urethra

Neuronal regulation of smooth muscle tone in the female pig urethra has mainly been studied in vitro using electrical field stimulation (EFS) of nerves. Excitatory control is considered to be exerted by released noradrenaline, whereas inhibitory control is non-adrenergic non-cholinergic (NANC), and mediated by nitric oxide (NO), and an as yet unidentified agent. We investigated the functional and morphological effects of α-latrotoxin (αLTX), a spider neurotoxin believed to cause massive release of vesicle-stored neurotransmitters, on spontaneously developed urethral smooth muscle tone. The effects were compared to those of EFS and high potassium. In the presence of the NO-synthesis inhibitor N^ω-nitro-L-arginine (L-NOARG: 0.3 mM) both αLTX and EFS evoked contractions. After treatment with scopolamine and phentolamine, no contraction was observed, and under these conditions αLTX and EFS induced relaxation. At low frequencies (<12 Hz), the EFS-induced relaxations were rapid, whereas at higher frequencies (>12 Hz), they were biphasic, consisting of a rapid first phase followed by a more long-lasting second phase. L-NOARG abolished the relaxations at low frequencies, as well as the first phase of the biphasic relaxation. The second phase was not affected by treatment with L-NOARG, but 0.1 μM ω-conotoxin GVIA, blocker of N-type voltage-operated calcium- channels (VOCCs), markedly reduced or abolished the response. In the presence of L-NOARG or ω-conotoxin GVIA, the αLTX-induced relaxation was significantly decreased, and the combination of L-NOARG and ω-conotoxin GVIA further reduced or abolished the relaxation. In preparationstreated with tetrodotoxin or scorpion venom, believed to inactivate nerves by acting on sodium channels, αLTX and EFS had no effects. αLTX-induced relaxation was not associated with changes in cyclic GMP or cyclic AMP content. High (80 mM) potassium solution induced a triphasic response of the preparation. A transient relaxation was followed by a restoration of tone, and then by a persistent relaxation. The persistent relaxation was slightly reduced by scorpion venom or L-NOARG, but reduced by 50% by a combination of L-NOARG and ω-conotoxin GVIA. Ultrastructural analysis of the urethral circular smooth muscle layer revealed a moderate amount of nerve profiles supplying the smooth muscle. In control preparations, the nerve profiles contained both small synaptic vesicles and large dense core vesicles. αLTX caused a major loss of both types of vesicle. The present data suggest that αLTX has the ability to release not only adrenergic and cholinergic transmitters, but also NANC mediators of relaxation, including NO, from nerve terminals in the urethra. Received: 13 January 1997 / Accepted: 17 April 1997