Pharmacology, 2019., Sep 12:1-9. doi: 10.1159/000502789.

Antihypertensive and Renoprotective Effects of Dietary Flaxseed and its Mechanism of Action in Deoxycorticosterone Acetate-Salt Hypertensive Rats.

Watanabe Y Ohata K Fukanoki A et al.

Abstract

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.

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Key Points

The deoxycorticosterone acetate (DOCA)-salt hypertensive rat is one of the most common experimental models for investigating antihypertensive action.  In the present study, the preventive effects of flaxseed powder, which includes ALA, lignans, and dietary fiber, and flaxseed oil, composed mainly of ALA, on the increase in blood pressure and induction of renal damage in DOCA-salt rats. It was confirmed that dietary flaxseed suppressed the development of hypertension in DOCA-salt rats. The concentration of flaxseed powder in the chow was 5% (w/w) in the low-powder group and 10% (w/w) in the high-powder group in this study. Therefore, the doses of flaxseed powder used in this study were reasonable for evaluating its effects on hypertension and renal damage in the rat model. In the current study, flaxseed oil suppressed the increase in ACE activity and inflammation-related gene expression observed in the DOCA-salt rat kidney, although it had no effects on the increase in oxidative stress-related factors.

In this study, flaxseed oil markedly suppressed the increase in proinflammatory cytokines and chemokines observed in DOCA-salt rats.  Flaxseed exhibited antihypertensive and renoprotective effects in DOCA-salt rats. Environmental stress-induced pressure was also attenuated by flaxseed. These effects were likely due to ALA. Furthermore, suppression of renal ACE activation, sympathetic nervous activation, and kidney and brain inflammation were suggested to be partially involved in the antihypertensive and renoprotective effects of flaxseed.