Effect of docosahexaenoic acid on smooth muscle cell functions

Hirafuji, Masahiko; Ebihara, Takashi; Kawahara, Fumito; Minami, Masaru

doi:10.1016/s0024-3205(98)00129-5

Cited by 16 publications

(10 citation statements)

References 15 publications

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“…DHA also suppresses Ca 2ϩ mobilization in smooth muscle cells. 33 DHA may have a direct relaxant action contributing to BP lowering. 34,35 DHA had no systemic effects on PRA or plasma aldosterone in Ang II-infused or control rats.…”

Section: Discussionmentioning

confidence: 99%

PPARα Activator Effects on Ang II–Induced Vascular Oxidative Stress and Inflammation

et al. 2002

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Abstract-Docosahexaenoic acid (DHA), a peroxisome proliferator-activated receptor-␣ (PPAR␣) activator, reduces blood pressure (BP) in some hypertensive models by unclear mechanisms. We tested the hypothesis that DHA would prevent BP elevation and improve vascular dysfunction in angiotensin (Ang) II-infused rats by modulating of NADPH oxidase activity and inflammation in vascular wall. Sprague-Dawley rats received Ang II (120 ng/kg per minute SC) with or without DHA (2.5 mL of oil containing 40% DHA/d PO) for 7 days. Systolic BP (mm Hg), elevated in Ang II-infused rats (172Ϯ3) versus controls (108Ϯ2, PϽ0.01), was reduced by DHA (112Ϯ4). In mesenteric small arteries studied in a pressurized myograph, media/lumen ratio was increased (PϽ0.05) and acetylcholine-induced relaxation impaired in Ang II-infused rats (PϽ0.05); both were normalized by DHA. In blood vessels of Ang II-infused rats, NADPH oxidase activity measured by chemiluminescence and expression of adhesion molecules intercellular adhesion molecule and vascular cell adhesion molecule-1 were significantly increased. These changes were abrogated by DHA. PPAR␣ activator DHA attenuated the development of hypertension, corrected structural abnormalities, and improved endothelial dysfunction induced by Ang II. These effects are associated with decreased oxidative stress and inflammation in the vascular wall.

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Section: Discussionmentioning

confidence: 99%

PPARα Activator Effects on Ang II–Induced Vascular Oxidative Stress and Inflammation

et al. 2002

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“…Because cftr Ϫ͞Ϫ mice do not express the cAMP-regulated chloride channel (36), it cannot be ruled out that oral DHA administration, at these high doses, also may be exerting its effect through a CFTR-independent mechanism. This may include the activation and͞or induction of other chloride conductance pathways (37), effects on other ion channels such as calcium (38,39), sodium (40), and potassium (41, Values for AA and DHA are expressed in nmol͞mg protein and for luminal diameter are expressed in m and represent the mean Ϯ SD from at least three separate experiments. LNA, ␣-linolenic acid.…”

Section: Discussionmentioning

confidence: 99%

A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr ^−/− mice

Freedman

Katz

Parker

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

272

239

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A deficiency in essential fatty acid metabolism has been reported in plasma from patients with cystic fibrosis (CF). However, its etiology and role in the expression of disease is unknown. The objective of this study was to determine whether alterations in fatty acid metabolism are specific to CF-regulated organs and whether they play a role in the expression of disease. A membrane lipid imbalance was found in ileum, pancreas, and lung from cftr ؊͞؊ mice characterized by an increase in phospholipid-bound arachidonic acid and a decrease in phospholipid-bound docosahexaenoic acid (DHA). This lipid imbalance was observed in organs pathologically affected by CF including lung, pancreas, and ileum and was not secondary to impaired intestinal absorption or hepatic biosynthesis of DHA. As proof of concept, oral administration of DHA to cftr ؊͞؊ mice corrected this lipid imbalance and reversed the observed pathological manifestations. These results strongly suggest that certain phenotypic manifestations of CF may result from remediable alterations in phospholipid-bound arachidonic acid and DHA levels.docosahexaenoic acid ͉ arachidonic acid ͉ fish oil ͉ pancreas ͉ lung C ystic fibrosis (CF) is the most prevalent lethal autosomal recessive disorder in the Caucasian population, affecting 1 in 2,500 newborns (1). Patients with CF express a typical phenotype characterized by pancreatic insufficiency, ileal hypertrophy, and recurrent pulmonary infections that ultimately lead to pulmonary failure and death. In 1989, the gene whose mutation results in CF was identified and cloned (2, 3). The product of the gene, the CF transmembrane conductance regulator (CFTR), was characterized as an ATP-gated chloride channel that is regulated by cAMP-dependent protein kinase phosphorylation (4).Despite the significant advances made in CF research in recent years, the mechanism by which a mutation in the CFTR gene leads to the manifestations of this disease remains unclear. Although a decrease in apical membrane CFTR-dependent chloride conductance might explain some of the pathological manifestations observed in CF, e.g., viscous secretions, it explains neither the increased inflammation in the lung nor the membrane-recycling defects observed in CF (5-7).Arachidonic acid (AA), an agonist of inflammatory pathways and a stimulant of mucus secretion, is elevated in the phospholipid fraction from bronchial alveolar lavage fluid in CF patients (5). However, the increased inflammation and elevated AA levels observed in CF have long been thought to be secondary to infection (8). This conclusion has been challenged recently by Heeckeren et al. (9), who demonstrated that instillation of agarose beads coated with Pseudomonas into the lungs of cftr Ϫ͞Ϫ mice resulted in increased inflammation and mortality compared with that observed in wild-type mice. These findings suggest that the lungs of cftr Ϫ͞Ϫ mice are primed for inflammation and that the increase in AA and inflammation observed in cftr Ϫ͞Ϫ mice may be a primary event and not secondary to infect...

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“…Other PUFA like DHA and eicosapentaenoic acid (EPA) seem to attenuate Ca 2+ signalling in different cells. Thus, Ca 2+ influx is suppressed by DHA in cardiac myocytes [69] and smooth muscle cells [70].…”

Section: Mechanisms Of Regulation Of Ca 2+mentioning

confidence: 94%

Regulation of intracellular calcium levels by polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid, in astrocytes: possible involvement of phospholipase A2

2005

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-Pathological conditions in the brain, such as ischemia, trauma and seizure are accompanied by increased levels of free n-6 and n-3 polyunsaturated fatty acids (PUFA), mainly arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA,. A neuroprotective role has been suggested for PUFA. For investigation of the potential molecular mechanisms involved in neuroprotection by PUFA, we studied the regulation of the concentration of intracellular Ca 2+ ([Ca 2+ ] i ) in rat brain astrocytes. We evaluated the presence of extracellular PUFA and the release of intracellular PUFA. Interestingly, only the constitutive brain PUFA AA and DHA, but not eicosapentaenoic acid (EPA) had prominent effects on intracellular Ca 2+ . AA and DHA suppressed [Ca 2+ ] i oscillation, inhibited store-operated Ca 2+ entry, and reduced the amplitudes of Ca 2+ responses evoked by agonists of G protein-coupled receptors. Moreover, prolonged exposure of astrocytes to AA and DHA brought the cells to a new steady state of a moderately elevated [Ca 2+ ] i level, where the cells became virtually insensitive to external stimuli. This new steady state can be considered as a mechanism of self-protection. It isolates disturbed parts of the brain, because AA and DHA reduce pathological overstimulation in the tissue surrounding the damaged area. In inflammation-related events, frequently AA and DHA exhibit opposite effects. However, in astrocytes AA and DHA exerted comparable effects on [Ca 2+ ] i . Extracellularly added AA and DHA, but not EPA, were also able to induce the release of [ 3 H]AA from prelabeled astrocytes. Therefore, we also suggest the involvement of phospholipase A 2 activation and lysophospholipid generation in the regulation of intracellular Ca 2+ in astrocytes.

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Effect of docosahexaenoic acid on smooth muscle cell functions

Cited by 16 publications

References 15 publications

PPARα Activator Effects on Ang II–Induced Vascular Oxidative Stress and Inflammation

PPARα Activator Effects on Ang II–Induced Vascular Oxidative Stress and Inflammation

A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr ^−/− mice

Regulation of intracellular calcium levels by polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid, in astrocytes: possible involvement of phospholipase A2

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Effect of docosahexaenoic acid on smooth muscle cell functions

Cited by 16 publications

References 15 publications

PPARα Activator Effects on Ang II–Induced Vascular Oxidative Stress and Inflammation

PPARα Activator Effects on Ang II–Induced Vascular Oxidative Stress and Inflammation

A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr −/− mice

Regulation of intracellular calcium levels by polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid, in astrocytes: possible involvement of phospholipase A2

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A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr ^−/− mice