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171.
B. Granstrm E. Nilsson U. Hultkvist‐Bengtsson L. Edvinsson 《Acta physiologica (Oxford, England)》2004,181(2):259-264
Aims and Methods: The pulmonary and vascular effects of endothelin‐1 receptor activation were studied in isolated perfused and ventilated lung preparations from rat. The responses to endothelin‐1 (ET‐1) and the endothelin B (ETB) receptor agonist sarafotoxin 6c (S6c) were characterized using the endothelin A (ETA)‐receptor antagonist FR 139317, the ETB‐receptor antagonist BQ 788 and the combined ETA/ETB‐receptor antagonist Bosentan. The respiratory parameter airway conductance (Gaw) and the vascular parameter perfusion flow were analysed simultaneously. Results: Concentration–response curves for ET‐1 administered intra‐arterially revealed that its most potent effect was on the vascular side while S6c had a more potent effect on airway conductance. ET‐1, given as a bolus dose intra‐arterially (100 μL of 0.2 nm ), induced a strong‐ and long‐lasting contraction of the vasculature while only a less pronounced contraction was seen in the airways. Neither of the antagonists had a significant effect per se on Gaw or perfusion flow. FR 139317 reduced the effect of ET‐1 on perfusion flow by about 50%, while airway conductance was augmented. BQ 788 enhanced the decrease in perfusion flow by ET‐1 while Gaw was not influenced. The combined ETA/ETB antagonist Bosentan powerfully prevented the ET‐1‐induced decrease in Gaw but did not alter its reduction in perfusion flow. Conclusions: The potent effect of ET‐1 on the vascular side of the lung is mediated mainly through ETA receptors, whereas both ETA and ETB receptors are involved in Gaw in the rat lung. 相似文献
172.
Millicent Ford Rauch Sara Royce Hynes James Bertram y Redmond Rebecca Robinson Cicely Williams Hao Xu Joseph A. Madri Erin B. Lavik 《The European journal of neuroscience》2009,29(1):132-145
Angiogenesis precedes recovery following spinal cord injury and its extent correlates with neural regeneration, suggesting that angiogenesis may play a role in repair. An important precondition for studying the role of angiogenesis is the ability to induce it in a controlled manner. Previously, we showed that a coculture of endothelial cells (ECs) and neural progenitor cells (NPCs) promoted the formation of stable tubes in vitro and stable, functional vascular networks in vivo in a subcutaneous model. We sought to test whether a similar coculture would lead to the formation of stable functional vessels in the spinal cord following injury. We created microvascular networks in a biodegradable two-component implant system and tested the ability of the coculture or controls (lesion control, implant alone, implant + ECs or implant + NPCs) to promote angiogenesis in a rat hemisection model of spinal cord injury. The coculture implant led to a fourfold increase in functional vessels compared with the lesion control, implant alone or implant + NPCs groups and a twofold increase in functional vessels over the implant + ECs group. Furthermore, half of the vessels in the coculture implant exhibited positive staining for the endothelial barrier antigen, a marker for the formation of the blood–spinal cord barrier. No other groups have shown positive staining for the blood–spinal cord barrier in the injury epicenter. This work provides a novel method to induce angiogenesis following spinal cord injury and a foundation for studying its role in repair. 相似文献
173.
大鼠抗GBM肾炎模型的建立及不同病期的生化指标和肾组织病理学观察 总被引:10,自引:4,他引:6
目的:为研究人类新月体抗肾炎的发病机制,建立大鼠抗肾小球基底膜(BGM)肾炎的动物模型,方法:提取S-D大鼠GBM抗原,将此抗原免疫新西兰白兔获得抗血清,再将此抗血清从尾静脉一次性注射给S-D大鼠。实验分2组:肾炎模型组及正常对照组。定期于第4天、第14天第第21天检测大鼠24h尿蛋白,血肌酐及血尿素的含量和肾组织病理学改变。结果:大鼠肾炎模型组:大鼠注射抗血清后于第4天出现大量蛋白尿,第14天血肌酐,血尿素显著升高,并持续上升,肾组织病理表现为肾小球内细胞数明显增加,大量新月体形成及蛋白管型,GBM呈不规则增厚,足突融合,内皮细胞脱落,坏死,免疫荧光检查见IgG、鼠IgG沿GBM线形分布,大鼠正常对照组以上指标均无明显改变。结论:通过动态观察大鼠抗GBM肾炎的病变变化,证实该模型病变与人类新月体性肾炎的病变较为一致,该模型可用于探讨人类新月体体肾炎的实验研究。 相似文献
174.
Mieczysaw Pokorski Zdzisaw Matysiak Magdalena Marczak Robert P. Ostrowski Andrzej Kapuciski Iwona Matuszewska Marianna Kaska Zbigniew Czarnocki 《Drug development research》2003,60(3):217-224
N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [3H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [3H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [3H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [3H]dopamine. Intravenous injections of [3H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [3H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc. 相似文献
175.
L. Wramner D. S. Robbins B. Kjellsson L. Mjörnstedt M. Olausson H. Brynger T. Söderström 《Transplant international》1990,3(1):55-58
Abstract. A single dose of rabbit antithymocyte globulin (ATG) was given as the sole immunosuppressive therapy in a model of strong MHC barrier rat heart allotransplantation. PVG/c hearts transplanted to Wistar/Kyoto (WKy) rats resulted in long-term surviving (LTS) grafts and cell-mediated lympholysis (CML) unresponsiveness in 50% of the animals. The effects of ATG treatment on the peripheral blood lymphocyte subsets were studied by flow cytometry. The absolute T-lymphocyte levels decreased to less than 5% and were normalized after 2 weeks. CD8-positive cells were normalized within 1 week, whereas CD4-and CD5-positive cells remained low. Rats with LTS grafts had low levels of all T-lymphocyte markers, especially the CD4-and CD5-positive cells. Rats rejecting their grafts showed an eightfold increase in levels of CD8-and CD5-positive lymphocytes and a twofold increase in levels of CD4-expressing lymphocytes. It is concluded that ATG treatment causes the immediate elimination of large lymphoid populations as well as long-lasting immunomodulation detectable in peripheral blood. 相似文献
176.
Zhen-yu Wu Laurent P. Rivory Michael S. Roberts 《Journal of pharmacokinetics and pharmacodynamics》1993,21(6):653-688
Distribution of Evans Blue (EB), sucrose, and water into the isolated perfused rat hindlimb was studied under various conditions using the multiple indicator dilution (MID) technique. Statistical moment analyses of the outflow profiles for the EB, sucrose, and water were used to define the vascular, extravascular, and total water spaces, respectively. The varied perfusion conditions included albumin content (2, 4.7, and 7%), temperature (25, 37, and 42 C), perfusate flow rate (2, 4, 8, and 12 ml/min) and the presence/absence of red blood cells. The range of studies undertaken were chosen to represent the variety of conditions used in the preparation of both isolated animal and human limbs, the latter being particularly important in cytotoxic therapy for recurrent malignant melanoma. The distribution volumes of EB, sucrose, and water were dependent on the flow rate and the albumin content of perfusate. The normalized variances (CV
2
) of the markers were of the following order: sucrose (2.18) > water (1.58) > EB (0.68), indicating that some disequilibrium occurs during the capillary exchange of water and sucrose. It is suggested that a Krebs-Henseleit buffer containing 2% BSA is a suitable perfusate for most studies of the isolated rat hindlimb perfusion. The effect of albumin concentration manifests itself only at higher flows.We acknowledge the support of the National Heart Foundation (Queensland) and the Mayne Bequest Foundation. This study was conducted while the investigator (Z.Y. Wu) was in receipt of a WHO Research Training Grant. Professor M. S. Roberts also acknowledges the support of the Queensland and Northern New South Wales Lions Kidney & Medical Research Foundation. 相似文献
177.
Chromosomal Mapping of Genetic Locus Associated with Thymus-size Enlargement in BUF/Mna Rats 总被引:2,自引:1,他引:1
Yoshiki Murakumo Masahide Takahashi Atsushi Arakawa Mitsuhiro Saito Hiroyuki Amo Hideki Katoh Mutsushi Matsuyama 《Cancer science》1993,84(8):838-840
The thymoma-prone rat of the BUF/Mna strain is a useful model for human thymoma. In this strain thymoma development is regulated by a single autosomal susceptible gene, Tsr-1. At pre-thymoma age, BUF/Mna rats have extremely large thyrauses, when compared to those of other strains of rats. Genetic studies in crosses between BUF/Mna rats with large thymuses and WKY/NCrj rats with small thymuses suggested the presence of a major autosomal gene, Ten-1 , which contributes to thymus enlargement in a backcross population. Linkage studies between Ten-1 and microsatellite markers in backcross rats of (WKY/NCrj×BUF/Mna)Fl×BUF/Mna have led to the localization of Ten-1 in chromosome 1. This result may provide an approach to clone Tsr-1 , which could be allelic to Ten-1. 相似文献
178.
Abstract. This study examined the ability of nitrova-sodilator treatment with isosorbide dinitrate to prevent the development of reduced nerve conduction velocity and nutritive blood flow in streptozotocin-induced diabetes mellitus in rats. Two month untreated diabetes caused approximately 23% and 13% reductions in sciatic motor and saphenous nerve sensory conduction velocity ( P < 0.001). Isosorbide dinitrate treatment provided 64.6 and 67.6% protection for motor and sensory nerves, respectively ( P < 0.01). Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and a hydrogen clearance technique. After 1 month untreated diabetes, flow was reduced by 41.9% ( P < 0.001). Isosorbide dinitrate treatment for 1 month in non-diabetic and diabetic rats significantly increased blood flow ( P < 0.01). When between-group variations in blood pressure were taken into account, vascular conductance increased by 29% and 31% in non-diabetic and diabetic rats, respectively ( P < 0.01). Thus, nitrovasodilator treatment improves nerve perfusion and function in experimental diabetes, probably by compensating for reduced endothelium-derived nitric oxide release or action. 相似文献
179.
MARTIN R. WILKINS LAN ZHAO & RIDA AL-TUBULY 《British journal of clinical pharmacology》1996,42(1):127-131
1 The ability to manipulate pharmacologically pulmonary vascular tone independent of effects on systemic blood vessels is a desirable objective. Elucidation of the biochemical mechanisms underlying hypoxia-induced pulmonary vasoconstriction (HPV) may permit preferential targeting of the pulmonary circulation.
2 Here we review our studies of the role of locally synthesized candidate vasoactive factors in HPV. In addition, we present data demonstrating an attenuated pressor response to hypoxia in the pulmonary circulation of Fischer 344 rats compared with the Wistar-Kyoto (WKY) rat strain.
3 We propose that a systematic genome-wide search using the HPV phenotype and a panel of highly informative microsatellite markers will elucidate the genetic loci underlying the difference in susceptibility to HPV in these two rat strains and provide a valuable and novel insight into the factors that determine the HPV response. 相似文献
2 Here we review our studies of the role of locally synthesized candidate vasoactive factors in HPV. In addition, we present data demonstrating an attenuated pressor response to hypoxia in the pulmonary circulation of Fischer 344 rats compared with the Wistar-Kyoto (WKY) rat strain.
3 We propose that a systematic genome-wide search using the HPV phenotype and a panel of highly informative microsatellite markers will elucidate the genetic loci underlying the difference in susceptibility to HPV in these two rat strains and provide a valuable and novel insight into the factors that determine the HPV response. 相似文献
180.
应用硫代乙酰胺灌胃复制暴发性肝功能衰竭大鼠模型,测定了大鼠胃肠推进运动的变化,结果:暴发性肝功能衰竭大鼠胃肠推进运动较正常大鼠显著减弱。肌肉注射胃复安、西沙必利或红霉素可显著增强肝功能衰竭大鼠的胃肠推进运动,这一效应可被皮下注射阿托品所完全阻断。表明这些药物可能通过迷走神经而使胃肠推进运动增强。 相似文献