Dietary fish oil improves endothelial function and lowers blood pressure via suppression of sphingolipid-mediated contractions in spontaneously hypertensive rats

Abstract

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.

Traditional Chinese medicine suppresses left ventricular hypertrophy by targeting extracellular signal-regulated kinases signaling pathway in spontaneously hypertensive rats

“…Interestingly, both BP reduction and LVH suppression were accompanied by favorable outcome in the present research. It was identified that SHR continued to develop further high BP level, which could also be seen in other studies on SHR model, leading to a higher incidence of LVH when compared with WKY rats 54 55 . Obvious formation of cardiac hypertrophy and over expression of EKR signaling pathway were identified in the C group.…”

Fish, Long-Chain n-3 PUFA and Incidence of Elevated Blood Pressure: A Meta-Analysis of Prospective Cohort Studies

“…Four previous meta-analyses of clinical trials showed that fish oil or LC n -3 PUFA supplements can dose-dependently lower BP in hypertensive patients but not in normotensive individuals [ 6 , 7 , 8 , 9 ]. However, investigations using animal models have shown that diets enriched in n -3 PUFA can protect against induced BP elevations [ 10 , 11 ], and dietary deficiency of n -3 PUFA in young rats was associated with development of hypertension in later life [ 12 ]. Some observational studies have reported that an inverse association between fish or LC n -3 PUFA consumption and BP elevations in normotensive participants [ 13 , 14 , 15 ], while others found no association [ 16 , 17 ].…”

n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: Principles, Practices, Pitfalls, and Promises - A Contemporary Review

“…By raising levels of adiponectin, n-3 PUFA indirectly cause additional NO expression. n-3 PUFA also protect the endothelium against angiotensin II-and glucose-mediated injury, lower membrane arachidonic acid content, and displace ceramide, thereby opposing ceramide signaling that induces vasoconstriction mediated by thromboxane [77]. Insertion of EPA into membranes interrupts waves of peroxidation, protects low-density lipoprotein cholesterol (LDL-C), and lowers the level of small, dense LDL-C (sdLDL), which itself causes endothelial dysfunction.…”