通过鱼油长期治疗增强大鼠颈动脉体内内皮损伤诱导的反应性降低。

Potentiation of the hyporeactivity induced by in vivo endothelial injury in the rat carotid artery by chronic treatment with fish oil.

作者信息

Joly G A, Schini V B, Hughes H, Vanhoutte P M

机构信息

Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030, USA.

出版信息

Br J Pharmacol. 1995 May;115(2):255-60. doi: 10.1111/j.1476-5381.1995.tb15871.x.

DOI:10.1111/j.1476-5381.1995.tb15871.x

PMID:7670727

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908320/

Abstract

The present study investigates whether or not chronic feeding of rats with a diet enriched in fish oil affects the reactivity of balloon-injured carotid arteries. The left carotid arteries were injured in vivo by the repeated passage of a balloon catheter. Both the right (control artery) and the left carotid arteries were excised 24 h after the injury, and suspended in organ chambers for the measurement of changes in isometric tension in the presence of indomethacin. 2. Phenylephrine evoked similar concentration-contraction curves in the right (control) carotid arteries without endothelium from control and fish oil-fed rats. Balloon injury decreased the contractility of carotid arteries to phenylephrine in both types of rats and the pEC50 for phenylephrine was significantly decreased in balloon-injured arteries from control rats compared to those obtained in arteries from fish oil-fed rats (pEC50 7.59 +/- 0.1 and 7.28 +/- 0.06, respectively) while maximal contractions were similar (1.93 +/- 0.15 g and 1.79 +/- 0.12 g, respectively). 3. The treatment of control right carotid arteries without endothelium with either NG-nitro-L-arginine (an inhibitor of nitric oxide synthase) or superoxide dismutase (which protects nitric oxide from degradation) did not affect significantly the contractions to phenylephrine in either group. In these preparations, methylene blue (an inhibitor of soluble guanylate cyclase) decreased slightly but significantly maximal contractions to phenylephrine in both groups. The treatment of balloon-injured carotid arteries with NG-nitro-L-arginine or methylene blue partly restored contractions to phenylephrine in arteries from both types of rat. Superoxide dismutase further depressed the contractility to the alpha l-adrenoceptor agonist in balloon-injured arteries from control diet-fed rats but had no effect in balloon-injured preparations from fish oil-fed rats.4. 3-Morpholino-sydnonimine (SIN-1, a donor of nitric oxide) evoked similar concentration-dependent relaxations in control and balloon-injured carotid arteries from both types of rat.5. Balloon injury caused an increase in the tissue content of cyclic GMP in carotid arteries from control diet-fed rats. This production of cyclic GMP was abolished by N0-nitro-L-arginine. Superoxide dismutase potentiated significantly the production of cyclic GMP caused by balloon injury in control but not in fish oil-fed rats.6 These observations confirm that in vivo balloon injury causes the production of nitric oxide in the injured blood vessel wall. This production of nitric oxide from L-arginine accounts for the decreased contractility to phenylephrine and the accumulation of cyclic GMP in balloon-injured arteries. They further indicate that chronic feeding of rats with fish oil potentiates the L-arginine-nitric oxide pathway in the injured vessel leading to an enhanced hyporeactivity to phenylephrine.

摘要

本研究旨在探讨长期给大鼠喂食富含鱼油的饮食是否会影响球囊损伤颈动脉的反应性。通过反复推送球囊导管在体内损伤大鼠的左颈动脉。损伤后24小时切除右（对照动脉）和左颈动脉，并将其悬挂在器官浴槽中，在吲哚美辛存在的情况下测量等长张力的变化。2. 去氧肾上腺素在对照组和喂食鱼油大鼠的无内皮右（对照）颈动脉中诱发相似的浓度-收缩曲线。球囊损伤降低了两种大鼠颈动脉对去氧肾上腺素的收缩性，与喂食鱼油大鼠的动脉相比，对照大鼠球囊损伤动脉中去氧肾上腺素的pEC50显著降低（分别为7.59±0.1和7.28±0.06），而最大收缩相似（分别为1.93±0.15 g和1.79±0.12 g）。3. 用NG-硝基-L-精氨酸（一氧化氮合酶抑制剂）或超氧化物歧化酶（保护一氧化氮不被降解）处理对照组无内皮的右颈动脉，对两组中去氧肾上腺素引起的收缩均无显著影响。在这些标本中，亚甲蓝（可溶性鸟苷酸环化酶抑制剂）使两组中去氧肾上腺素引起的最大收缩略有但显著降低。用NG-硝基-L-精氨酸或亚甲蓝处理球囊损伤的颈动脉，部分恢复了两种大鼠动脉对去氧肾上腺素的收缩。超氧化物歧化酶进一步降低了对照饮食喂养大鼠球囊损伤动脉对α1-肾上腺素能激动剂的收缩性，但对喂食鱼油大鼠的球囊损伤标本无影响。4. 3-吗啉代-西多胺（SIN-1，一种一氧化氮供体）在两种大鼠的对照和球囊损伤颈动脉中诱发相似的浓度依赖性舒张。5. 球囊损伤导致对照饮食喂养大鼠颈动脉中环鸟苷酸的组织含量增加。这种环鸟苷酸的产生被N0-硝基-L-精氨酸消除。超氧化物歧化酶显著增强了对照大鼠球囊损伤引起的环鸟苷酸的产生，但对喂食鱼油大鼠无此作用。6. 这些观察结果证实，体内球囊损伤导致损伤血管壁中一氧化氮的产生。这种由L-精氨酸产生的一氧化氮导致球囊损伤动脉中对去氧肾上腺素的收缩性降低和环鸟苷酸的积累。它们进一步表明，长期给大鼠喂食鱼油可增强损伤血管中L-精氨酸-一氧化氮途径，导致对去氧肾上腺素的反应性降低增强。