Effects of Docosahexaenoic Acid on Vascular Pathology and Reactivity in Hypertension

Abstract

Previous studies have shown that docosahexaenoic acid (DHA) has an antihypertensive effect in spontaneously hypertensive rats (SHR). To investigate possible mechanisms for this effect, vascular pathology and reactivity were determined in SHR treated with dietary DHA. SHR (7 weeks) were fed a purified diet with either a combination of corn/soybean oils or a DHA-enriched oil for 6 weeks. Histological evaluation of heart tissue, aorta, coronary, and renal arteries was performed. Vascular responses were determined in isolated aortic rings. Contractile responses to agonists, including norepinephrine (10(-9) to 10(-4) M), potassium chloride (5-55 mM), and angiotensin II (5 x 10(-7) M) were assessed. Vasorelaxant responses to acetylcholine (10(-9) to 10 (-4) M), sodium nitroprusside (10(-9) to 10(-6) M), papaverine (10(-5) to 10(-4) M), and methoxyverapamil (D600, 1-100 microM) were determined. DHA-fed SHR had significantly reduced blood pressure (P < 0.001) and vascular wall thicknesses in the coronary, thoracic, and abdominal aorta compared with controls (P < 0.05) Contractile responses to agonists mediated by receptor stimulation and potassium depolarization were not altered in DHA-fed SHR. Endothelial-dependent relaxations to acetylcholine were not altered which suggests endothelial-derived nitric oxide production/release is not affected by dietary DHA. Other mechanisms of vascular relaxation, including intracellular cyclic nucleotides, cGMP, and cAMP were not altered by dietary DHA because aortic relaxant responses to sodium nitroprusside and papaverine were similar in control and DHA-fed SHR. No significant differences were seen in relaxant responses to the calcium channel blocker, D600, or contractile responses to norepinephrine in the absence of extracellular calcium. These results suggest that dietary DHA does not affect mechanisms related to extracellular calcium channels or intracellular calcium mobilization. Moreover, the contractile and vasorelaxant responses are not differentially altered with dietary DHA in this in vivo SHR model. The findings demonstrate that dietary DHA reduces systolic blood pressure and vascular wall thickness in SHR. This may contribute to decrease arterial stiffness and pulse pressure, in addition to the antihypertensive properties of DHA. The antihypertensive properties of DHA are not related to alterations in vascular responses.

Fish oil supplementation improves large arterial elasticity in overweight hypertensive patients

“…Moreover, there is a clinical trial that also favors the mechanism based on the relationship between low serum EPA to arachidonic acid ratio and arterial stiffness in community-dwelling elderly (Tomio et al, 2002). However, Engler et al (2003) showed that DHA-fed spontaneous hypertensive rat had improved arterial elasticity which related not to the change of contractile and vasorelaxant responses of arteries, but to the reduced BP and vascular wall thicknesses.…”

The differential effects of EPA and DHA on cardiovascular risk factors

“…In addition, EPA was shown to increase acetylcholine-induced endothelium-dependent hyperpolarising factor-mediated vasodilation in diabetic rats (125) . Endothelium-independent vasodilatory effects are mediated by the modulation of Ca 2 + signalling in smooth muscle cells, but the mechanisms, especially with respect to the type of Ca channels involved, remain uncertain (126)(127)(128)(129) . AA, EPA and DHA are also substrates for the CYP450 enzymes that act as monooxygenases, catalysing hydroxylation, epoxidation or allylic oxidation.…”

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

“…In animal studies, DHA reduces systolic blood pressure and vascular wall thickness in spontaneously hypertensive rats25, 62 and aldosterone‐induced hypertension in dogs 27. Our study, however, is the first to elucidate the hypotensive effects of DHA in experimental atherosclerosis induced in mice by feeding a Western diet.…”

“…Clinical trials in post–myocardial infarction patients have suggested that DHA, specifically, may exert a therapeutic effect, particularly on hypertension and the risk of reinfarction,22 although this has not been shown unequivocally or linked with atherosclerotic plaque stabilization/regression 23, 24. DHA supplementation decreased blood pressure in spontaneously hypertensive rats25, 26 and in a dog model of hypertension,27 but no data are available for mouse models with atherosclerosis.…”