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一氧化氮合酶抑制剂长期治疗对清醒布氏大鼠局部血流动力学对血管舒张剂反应的影响。

Effects of chronic treatment with nitric oxide synthase inhibitors on regional haemodynamic responses to vasodilators in conscious Brattleboro rats.

作者信息

Gardiner S M, Kemp P A, Bennett T

机构信息

Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre.

出版信息

Br J Pharmacol. 1993 May;109(1):222-8. doi: 10.1111/j.1476-5381.1993.tb13557.x.

DOI:10.1111/j.1476-5381.1993.tb13557.x
PMID:7684304
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2175574/
Abstract
  1. The effects of acute inhibition of nitric oxide (NO) synthase on cardiovascular responses to vasodilator challenges have already been described. We now report the responses to vasodilators during and after chronic NO synthase inhibition. 2. In conscious Brattleboro rats, the regional haemodynamic effects of 3 min infusions of acetylcholine (4 micrograms min-1), sodium nitroprusside (15 micrograms min-1) or adrenaline (0.2 micrograms min-1) were assessed (from areas under or over curves (AUC, AOC)) under control conditions, 6 and 72 h after the addition of the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) to the drinking water (1 mg ml-1), and 6, 24 and 48 h after the withdrawal of L-NMMA. In a separate group of Brattleboro rats, responses to acetylcholine, sodium nitroprusside and adrenaline were assessed before and 6 h after the onset of oral ingestion of the more potent nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.05 mg ml-1). 3. Acetylcholine caused renal vasodilation (87 +/- 11 units) and mesenteric vasoconstriction (-31 +/- 5 units), sodium nitroprusside caused vasodilatation in renal (96 +/- 12 units), mesenteric (222 +/- 13 units) and hindquarters (49 +/- 15 units) vascular beds, whereas adrenaline caused hindquarters vasodilatation (92 +/- 8 units). Seventy two h after the onset of oral ingestion of L-NMMA, acetylcholine had a decreased renal vasodilator (59 +/- 9 units) effect, sodium nitroprusside had an increased renal vasodilator (142 +/- 23 units) action, while adrenaline had a decreased hindquarters vasodilator (55 +/- 6 units) influence. Twenty four h after withdrawal of L-NMMA, the renal vasodilator effect of acetylcholine was greater than the control response (106 +/- 14 units), but the regional haemodynamic effects of sodium nitroprusside and adrenaline were not different from those under control conditions. Hence, the increased renal vasodilator response to acetylcholine was probably due to changes in muscarinic receptor-mediated mechanisms rather than to any increase in guanylyl cyclase or its sensitivity to NO.
摘要
  1. 一氧化氮（NO）合酶急性抑制对心血管系统对血管舒张剂刺激反应的影响已有报道。我们现在报告慢性NO合酶抑制期间及之后对血管舒张剂的反应。2. 在清醒的布拉特洛维大鼠中，评估了在对照条件下、向饮用水中添加NO合酶抑制剂NG-单甲基-L-精氨酸（L-NMMA，1mg/ml）后6小时和72小时以及撤去L-NMMA后6小时、24小时和48小时，静脉输注乙酰胆碱（4μg/min）、硝普钠（15μg/min）或肾上腺素（0.2μg/min）3分钟的局部血流动力学效应（根据曲线下或曲线上面积（AUC，AOC））。在另一组布拉特洛维大鼠中，评估了口服更有效的NO合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME，0.05mg/ml）前及开始口服后6小时对乙酰胆碱、硝普钠和肾上腺素的反应。3. 乙酰胆碱引起肾血管舒张（87±11单位）和肠系膜血管收缩（-31±5单位），硝普钠引起肾（96±12单位）、肠系膜（222±13单位）和后肢（49±15单位）血管床血管舒张，而肾上腺素引起后肢血管舒张（92±8单位）。口服L-NMMA 72小时后，乙酰胆碱的肾血管舒张作用减弱（59±9单位），硝普钠的肾血管舒张作用增强（142±23单位），而肾上腺素的后肢血管舒张作用减弱（55±6单位）。撤去L-NMMA 24小时后，乙酰胆碱的肾血管舒张作用大于对照反应（106±14单位），但硝普钠和肾上腺素的局部血流动力学效应与对照条件下无差异。因此，乙酰胆碱肾血管舒张反应增强可能是由于毒蕈碱受体介导机制的改变，而非鸟苷酸环化酶增加或其对NO敏感性增加所致。

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Regional blood flow measurement with pulsed Doppler flowmeter in conscious rat.清醒大鼠中使用脉冲多普勒流量计测量局部血流
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Friedman and Quade tests: BASIC computer program to perform nonparametric two-way analysis of variance and multiple comparisons on ranks of several related samples.弗里德曼检验和奎德检验：用于对多个相关样本的秩进行非参数双向方差分析和多重比较的BASIC计算机程序。
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L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro.L-NG-硝基精氨酸（L-NOARG），一种新型的、体外可逆转内皮依赖性血管舒张的L-精氨酸抑制剂。
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Regional haemodynamic changes during oral ingestion of NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester in conscious Brattleboro rats.清醒的遗传性高血压大鼠口服NG-单甲基-L-精氨酸或NG-硝基-L-精氨酸甲酯期间的局部血流动力学变化
Br J Pharmacol. 1990 Sep;101(1):10-2. doi: 10.1111/j.1476-5381.1990.tb12079.x.
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Can pulsed Doppler technique measure changes in aortic blood flow in conscious rats?脉冲多普勒技术能否测量清醒大鼠的主动脉血流变化？
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Nitric oxide: physiology, pathophysiology, and pharmacology.一氧化氮：生理学、病理生理学与药理学
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Development and mechanism of a specific supersensitivity to nitrovasodilators after inhibition of vascular nitric oxide synthesis in vivo.体内血管一氧化氮合成受抑制后对硝基血管扩张剂产生特异性超敏反应的发展及机制
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