Background/Aims: Flaxseed contains alpha-linolenic acid (ALA), lignans, and dietary fiber, and its intake lowers blood pressure in hypertensive patients. Here, we examined the effects of flaxseed powder, which includes all flaxseed components, flaxseed oil, composed mainly of ALA, flaxseed lignan, and flaxseed fiber, on hypertension and renal damage induced by deoxycorticosterone acetate (DOCA)-salt. Then, we investigated the mechanisms of action associated with the effects of flaxseed. Methods: Flaxseed powder, oil, lignan, or fiber was administered to DOCA-salt rats. Systolic blood pressure (SBP), urinary protein excretion, renal angiotensin converting enzyme (ACE) activity, sympathetic nerve activity, and gene expression of inflammatory mediators in the kidney and hypothalamus were measured. Results: Flaxseed powder and oil reduced the increases in SBP and urinary protein excretion induced by DOCA-salt treatment, whereas lignan and fiber had no effects. Flaxseed oil suppressed the increase in renal ACE activity, sympathetic nerve activity, and gene expression of renal and hypothalamic inflammatory mediators. Conclusion: Flaxseed has antihypertensive and renoprotective effects in DOCA-salt rats. These effects are likely principally exerted by ALA. Furthermore, the suppression of renal ACE activity, sympathetic nerve activity, and inflammation is partly involved in the effects of flaxseed.

1.
Ferrara LA, Ricci F, Viola S, DE Luca G, Ferrara F, DI Fronzo V, et al. Dietary pattern and blood pressure control in a hypertension outpatient clinic.
Hypertens Res
. 2007 Nov;30(11):1043–50.
2.
Kawamura A, Kajiya K, Kishi H, Inagaki J, Mitarai M, Oda H, et al. Effects of the DASH-JUMP dietary intervention in Japanese participants with high-normal blood pressure and stage 1 hypertension: an open-label single-arm trial.
Hypertens Res
. 2016 Nov;39(11):777–85.
3.
Rodriguez-Leyva D, Weighell W, Edel AL, LaVallee R, Dibrov E, Pinneker R, et al. Potent antihypertensive action of dietary flaxseed in hypertensive patients.
Hypertension
. 2013 Dec;62(6):1081–9.
4.
Al-Bishri WM. Favorable effects of flaxseed supplemented diet on liver and kidney functions in hypertensive Wistar rats.
J Oleo Sci
. 2013;62(9):709–15.
5.
Velasquez MT, Bhathena SJ, Ranich T, Schwartz AM, Kardon DE, Ali AA, et al. Dietary flaxseed meal reduces proteinuria and ameliorates nephropathy in an animal model of type II diabetes mellitus.
Kidney Int
. 2003 Dec;64(6):2100–7.
6.
Prasad K. Flaxseed and cardiovascular health.
J Cardiovasc Pharmacol
. 2009 Nov;54(5):369–77.
7.
Ogawa A, Suzuki Y, Aoyama T, Takeuchi H. Dietary alpha-linolenic acid inhibits angiotensin-converting enzyme activity and mRNA expression levels in the aorta of spontaneously hypertensive rats.
J Oleo Sci
. 2009;58(7):355–60.
8.
Prasad K. Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed, an Alternative to ACE Inhibitors in the Treatment of Hypertension.
Int J Angiol
. 2013 Dec;22(4):235–8.
9.
Sánchez D, Quiñones M, Moulay L, Muguerza B, Miguel M, Aleixandre A. Changes in arterial blood pressure of a soluble cocoa fiber product in spontaneously hypertensive rats.
J Agric Food Chem
. 2010 Feb;58(3):1493–501.
10.
Seifi B, Kadkhodaee M, Zahmatkesh M, Golab F, Bakhshi E. Changes in serum and renal vitamin E levels in deoxycorticosterone acetate-salt hypertensive rats.
Transplant Proc
. 2009 Sep;41(7):2910–1.
11.
Toba H, Yoshida M, Tojo C, Nakano A, Oshima Y, Kojima Y, et al. L/N-type calcium channel blocker cilnidipine ameliorates proteinuria and inhibits the renal renin-angiotensin-aldosterone system in deoxycorticosterone acetate-salt hypertensive rats.
Hypertens Res
. 2011 Apr;34(4):521–9.
12.
Wang D, Luo Y, Myakala K, Orlicky DJ, Dobrinskikh E, Wang X, et al. Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats.
Sci Rep
. 2017 Aug;7(1):9793.
13.
Basting T, Lazartigues E. DOCA-Salt Hypertension: an Update.
Curr Hypertens Rep
. 2017 Apr;19(4):32.
14.
Xia H, Sriramula S, Chhabra KH, Lazartigues E. Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension.
Circ Res
. 2013 Oct;113(9):1087–96.
15.
Sriramula S, Xia H, Xu P, Lazartigues E. Brain-targeted angiotensin-converting enzyme 2 overexpression attenuates neurogenic hypertension by inhibiting cyclooxygenase-mediated inflammation.
Hypertension
. 2015 Mar;65(3):577–86.
16.
Guyenet PG. The sympathetic control of blood pressure.
Nat Rev Neurosci
. 2006 May;7(5):335–46.
17.
Waki H, Gouraud SS. Brain inflammation in neurogenic hypertension.
World J Hypertens
. 2014;4(1):1–6.
18.
Fujita H, Takeda K, Miki S, Morimoto S, Kawa T, Uchida A, et al. Chronic angiotensin blockade with candesartan cilexetil in DOCA/salt hypertensive rats reduces cardiac hypertrophy and coronary resistance without affecting blood pressure.
Hypertens Res
. 1997 Dec;20(4):263–7.
19.
Oliveira-Sales EB, Toward MA, Campos RR, Paton JF. Revealing the role of the autonomic nervous system in the development and maintenance of Goldblatt hypertension in rats.
Auton Neurosci
. 2014 Jul;183:23–9.
20.
Toba H, Wang J, Ohigashi M, Kobara M, Nakata T. Telmisartan protects against vascular dysfunction with peroxisome proliferator-activated receptor-γ activation in hypertensive 5/6 nephrectomized rats.
Pharmacology
. 2013;92(5-6):265–75.
21.
Ohigashi M, Imai N, Toba H, Kobara M, Nakata T. Pitavastatin Exhibits Protective Effects on Podocytes Accompanied by BMP-7 Up-Regulation and Rho Suppression.
Pharmacology
. 2016;97(5-6):265–76.
22.
Wang J, Toba H, Morita Y, Nakashima K, Noda K, Tian W, et al. Endothelial dysfunction, macrophage infiltration and NADPH oxidase-dependent superoxide production were attenuated by erythropoietin in streptozotocin-induced diabetic rat aorta.
Pharmacology
. 2013;91(1-2):48–58.
23.
Xu Z, Li W, Han J, Zou C, Huang W, Yu W, et al. Angiotensin II induces kidney inflammatory injury and fibrosis through binding to myeloid differentiation protein-2 (MD2).
Sci Rep
. 2017 Mar;7(1):44911.
24.
Benigni A, Cassis P, Remuzzi G. Angiotensin II revisited: new roles in inflammation, immunology and aging.
EMBO Mol Med
. 2010 Jul;2(7):247–57.
25.
Peng H, Carretero OA, Alfie ME, Masura JA, Rhaleb NE. Effects of angiotensin-converting enzyme inhibitor and angiotensin type 1 receptor antagonist in deoxycorticosterone acetate-salt hypertensive mice lacking Ren-2 gene.
Hypertension
. 2001 Mar;37(3):974–80.
26.
Kumar KV, Das UN. Effect of cis-unsaturated fatty acids, prostaglandins, and free radicals on angiotensin-converting enzyme activity in vitro.
Proc Soc Exp Biol Med
. 1997 Apr;214(4):374–9.
27.
Ulu A, Harris TR, Morisseau C, Miyabe C, Inoue H, Schuster G, et al. Anti-inflammatory effects of ω-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension.
J Cardiovasc Pharmacol
. 2013 Sep;62(3):285–97.
28.
Reid JL, Zivin JA, Kopin IJ. Central and peripheral adrenergic mechanisms in the development of deoxycorticosterone-saline hypertension in rats.
Circ Res
. 1975 Nov;37(5):569–79.
29.
Mu S, Shimosawa T, Ogura S, Wang H, Uetake Y, Kawakami-Mori F, et al. Epigenetic modulation of the renal β-adrenergic-WNK4 pathway in salt-sensitive hypertension.
Nat Med
. 2011 May;17(5):573–80.
30.
Yemane H, Busauskas M, Burris SK, Knuepfer MM. Neurohumoral mechanisms in deoxycorticosterone acetate (DOCA)-salt hypertension in rats.
Exp Physiol
. 2010 Jan;95(1):51–5.
31.
Patrick RP, Ames BN. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior.
FASEB J
. 2015 Jun;29(6):2207–22.
32.
Molderings GJ, Werner K, Likungu J, Göthert M. Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein via presynaptic 5-HT receptors similar to the 5-HT 1D subtype.
Naunyn Schmiedebergs Arch Pharmacol
. 1990 Oct;342(4):371–7.
33.
Molderings GJ, Fink K, Schlicker E, Göthert M. Inhibition of noradrenaline release via presynaptic 5-HT1B receptors of the rat vena cava.
Naunyn Schmiedebergs Arch Pharmacol
. 1987 Sep;336(3):245–50.
34.
Kim KI, Lee JH, Chang HJ, Cho YS, Youn TJ, Chung WY, et al. Association between blood pressure variability and inflammatory marker in hypertensive patients.
Circ J
. 2008 Feb;72(2):293–8.
35.
Pruijm M, Vollenweider P, Mooser V, Paccaud F, Preisig M, Waeber G, et al. Inflammatory markers and blood pressure: sex differences and the effect of fat mass in the CoLaus Study.
J Hum Hypertens
. 2013 Mar;27(3):169–75.
36.
Sesso HD, Buring JE, Rifai N, Blake GJ, Gaziano JM, Ridker PM. C-reactive protein and the risk of developing hypertension.
JAMA
. 2003 Dec;290(22):2945–51.
37.
Santisteban MM, Ahmari N, Carvajal JM, Zingler MB, Qi Y, Kim S, et al. Involvement of bone marrow cells and neuroinflammation in hypertension.
Circ Res
. 2015 Jul;117(2):178–91.
38.
Shi P, Diez-Freire C, Jun JY, Qi Y, Katovich MJ, Li Q, et al. Brain microglial cytokines in neurogenic hypertension.
Hypertension
. 2010 Aug;56(2):297–303.
39.
Clarkson BD, Kahoud RJ, McCarthy CB, Howe CL. Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons.
Sci Rep
. 2017 Aug;7(1):9037.
40.
Yip PK, Pizzasegola C, Gladman S, Biggio ML, Marino M, Jayasinghe M, et al. The omega-3 fatty acid eicosapentaenoic acid accelerates disease progression in a model of amyotrophic lateral sclerosis.
PLoS One
. 2013 Apr;8(4):e61626.
41.
Belayev L, Khoutorova L, Atkins KD, Eady TN, Hong S, Lu Y, et al. Docosahexaenoic Acid therapy of experimental ischemic stroke.
Transl Stroke Res
. 2011 Mar;2(1):33–41.
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