膳食鱼油通过抑制自发性高血压大鼠中鞘脂介导的收缩来改善内皮功能并降低血压。
Dietary fish oil improves endothelial function and lowers blood pressure via suppression of sphingolipid-mediated contractions in spontaneously hypertensive rats.
作者信息
van den Elsen Lieke W J, Spijkers Léon J A, van den Akker Rob F P, van Winssen Aggie M H, Balvers Martin, Wijesinghe Dayanjan S, Chalfant Charles E, Garssen Johan, Willemsen Linette E M, Alewijnse Astrid E, Peters Stephan L M
机构信息
aDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht bDivision of Pharmacology & Pharmacotherapy, Academic Medical Center, Amsterdam cNutricia Research, Centre for Specialised Nutrition, Utrecht, The Netherlands dHunter Holmes McGuire Veterans Administration Medical Center eDepartment of Biochemistry & Molecular Biology, Virginia Commonwealth University fVirginia Commonwealth University Reanimation Engineering Science Center (VCURES) gThe Massey Cancer Center, Richmond, Virginia, USA.
出版信息
J Hypertens. 2014 May;32(5):1050-8; discussion 1058. doi: 10.1097/HJH.0000000000000131.
OBJECTIVE
Long-chain n-3 polyunsaturated fatty acids from oily fish reduce blood pressure (BP) in hypertension. Previously, we demonstrated that hypertension is associated with marked alterations in sphingolipid biology and elevated ceramide-induced vasoconstriction. Here we investigated in spontaneously hypertensive rats (SHRs) whether fish oil improves endothelial function including reduced vascular contraction induced via the sphingolipid cascade, resulting in reduced BP.
METHODS
Twelve-week-old SHRs were fed a control or fish oil-enriched diet during 12 weeks, and BP was recorded. Plasma sphingolipid levels were quantified by mass spectrometry and the response of isolated carotid arteries towards different stimuli was measured. Furthermore, erythrocyte membrane fatty acid composition, thromboxane A2 formation and cytokine secretion in ex-vivo lipopolysaccharide-stimulated thoracic aorta segments were determined.
RESULTS
The fish oil diet reduced the mean arterial BP (P < 0.001) and improved endothelial function, as indicated by a substantially increased relaxation potential towards ex-vivo methacholine exposure of the carotid arteries (P < 0.001). The long-chain n-3 polyunsaturated fatty acid diet resulted in altered levels of specific (glucosyl)ceramide subspecies (P < 0.05), reduced membrane arachidonic acid content (P < 0.001) and decreased thromboxane concentrations in plasma (P < 0.01). Concomitantly, the fish oil diet largely reduced ceramide-induced contractions (P < 0.01), which are predominantly mediated by thromboxane. Furthermore, thromboxane A2 and interleukin-10 were reduced in supernatants of lipopolysaccharide-stimulated thoracic aorta of SHRs fed the fish oil diet while RANTES (regulated on activation, normal T-cell expressed and secreted) was enhanced. This may contribute to reduced vasoconstriction in vivo.
CONCLUSIONS
Dietary fish oil lowers BP in SHRs and improves endothelial function in association with suppression of sphingolipid-dependent vascular contraction.
目的
油性鱼类中的长链n-3多不饱和脂肪酸可降低高血压患者的血压（BP）。此前，我们证明高血压与鞘脂生物学的显著改变以及神经酰胺诱导的血管收缩增强有关。在此，我们研究了鱼油是否能改善自发性高血压大鼠（SHR）的内皮功能，包括减少通过鞘脂级联反应诱导的血管收缩，从而降低血压。
方法
12周龄的SHR在12周内分别喂食对照饮食或富含鱼油的饮食，并记录血压。通过质谱法定量血浆鞘脂水平，并测量离体颈动脉对不同刺激的反应。此外，还测定了红细胞膜脂肪酸组成、血栓素A2的形成以及体外脂多糖刺激的胸主动脉段中的细胞因子分泌。
结果
鱼油饮食降低了平均动脉血压（P<0.001），并改善了内皮功能，这表现为离体颈动脉对乙酰甲胆碱暴露的舒张潜能显著增加（P<0.001）。长链n-3多不饱和脂肪酸饮食导致特定（葡萄糖基）神经酰胺亚类水平改变（P<0.05），膜花生四烯酸含量降低（P<0.001），血浆中血栓素浓度降低（P<0.01）。同时，鱼油饮食在很大程度上减少了神经酰胺诱导的收缩（P<0.01），这种收缩主要由血栓素介导。此外，在喂食鱼油饮食的SHR的脂多糖刺激的胸主动脉上清液中，血栓素A2和白细胞介素-10减少，而调节激活正常T细胞表达和分泌的趋化因子（RANTES）增加。这可能有助于体内血管收缩的减少。
结论
饮食中的鱼油可降低SHR的血压，并与抑制鞘脂依赖性血管收缩相关联地改善内皮功能。
Zotero 插件