在高胆固醇血症兔中，在激动剂诱发的内皮舒张因子（EDRF）释放之前，流量依赖性EDRF释放就已被消除。

Abolition of flow-dependent EDRF release before that evoked by agonists in hypercholesterolaemic rabbits.

作者信息

Hutcheson I R, Smith J A, Griffith T M

机构信息

Department of Diagnostic Radiology, University of Wales College of Medicine, Heath Park, Cardiff.

出版信息

Br J Pharmacol. 1994 Sep;113(1):190-4. doi: 10.1111/j.1476-5381.1994.tb16192.x.

DOI:10.1111/j.1476-5381.1994.tb16192.x

PMID:7529109

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1510044/

Abstract

We have used a pulsatile cascade bioassay system to investigate the effects of dietary-induced hypercholesterolaemia on EDRF release evoked by acetylcholine and by the oscillatory and time-averaged components of flow, in isolated segments of rabbit abdominal aorta. 2. Flow pulsatility (frequency range 0.1-10 Hz) was studied with constant flow (9 ml min-1) at a pulse pressure amplitude of 2 mmHg. Frequency-related EDRF release, maximal at 6 Hz, was slightly attenuated after 4 weeks and abolished after 8 weeks of cholesterol feeding. 3. Time-averaged shear stress was manipulated with dextran (1-4% w/v, 80000 mol. wt.), to increase perfusate viscosity. EDRF release induced by increased perfusate viscosity was unaffected after 4 weeks but abolished after 8 weeks of cholesterol feeding. 4. Endothelium-dependent relaxations to acetylcholine (0.1-10 microM) were not influenced after 4 weeks and only partially attenuated (by 60% of the maximal response, EC50 unchanged at 6.45 +/- 0.04 vs. 6.4 +/- 0.1 microM) after 8 weeks of cholesterol feeding. 5. Blood cholesterol levels were significantly (P < 0.001) increased after 4 weeks (26 +/- 3.6 vs 2.6 +/- 0.6 mmol l-1) and 8 weeks (56.2 +/- 3.8 vs 1.3 +/- 0.1 mmol l-1) of cholesterol feeding but after 8 weeks plasma L-arginine levels were not significantly different from the age-matched controls (0.2 +/- 0.05 vs. 0.19 +/- 0.04 mmol l-1). 6. We conclude that hypercholesterolaemia impairs flow-related (pulsatile- and time-averaged shear-induced) EDRF release earlier than acetylcholine-induced relaxation in rabbit aorta. This is consistent with the view that different transduction mechanisms mediate EDRF release in response to agonists and flow.

摘要

我们使用了一种搏动性级联生物测定系统，以研究饮食诱导的高胆固醇血症对兔腹主动脉分离段中乙酰胆碱以及血流振荡和时间平均成分所诱发的内皮舒张因子（EDRF）释放的影响。2. 在2 mmHg的脉压幅度下，以恒定流量（9 ml·min⁻¹）研究流量搏动性（频率范围0.1 - 10 Hz）。与频率相关的EDRF释放在6 Hz时最大，在胆固醇喂养4周后略有减弱，8周后消失。3. 用右旋糖酐（1 - 4% w/v，80000 mol·wt.）控制时间平均剪切应力，以增加灌注液粘度。灌注液粘度增加所诱导的EDRF释放在胆固醇喂养4周后未受影响，但8周后消失。4. 对乙酰胆碱（0.1 - 10 μM）的内皮依赖性舒张在4周后未受影响，在胆固醇喂养8周后仅部分减弱（最大反应减弱60%，半数有效浓度（EC50）在6.45 ± 0.04 μM与6.4 ± 0.1 μM时无变化）。5. 胆固醇喂养4周（26 ± 3.6 vs 2.6 ± 0.6 mmol·l⁻¹）和8周（56.2 ± 3.8 vs 1.3 ± 0.1 mmol·l⁻¹）后，血液胆固醇水平显著升高（P < 0.001），但8周后血浆L - 精氨酸水平与年龄匹配的对照组无显著差异（0.2 ± 0.05 vs. 0.19 ± 0.04 mmol·l⁻¹）。6. 我们得出结论，在兔主动脉中，高胆固醇血症比乙酰胆碱诱导的舒张更早损害与血流相关的（搏动性和时间平均剪切诱导的）EDRF释放。这与不同转导机制介导EDRF对激动剂和血流反应释放的观点一致。