Docosahexaenoic Acid is an Antihypertensive Nutrient That Affects Aldosterone Production in SHR

Abstract

The effects of dietary docosahexaenoic acid (DHA), an -3 polyunsaturated fatty acid, on blood pressure and some pressure-regulating systems were measured in young spontaneously hypertensive rats (SHR). Plasma aldosterone and corticosterone levels, adrenal aldosterone production in vitro, and characteristics of adrenal angiotensin receptors were measured after 6 weeks of diet. Renal cytochrome P450 (CYP) 4A gene expression and arachidonic acid metabolism by renal microsomes were also investigated. Plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured. Diets contained either corn/soybean oil alone (CSO), or oil enriched with DHA. After 6 weeks, rats fed DHA had systolic blood pressures averaging 34 mmHg less than controls (P < 0.001). Plasma aldosterone levels were 33% lower in the DHA-fed animals than in controls (22 ± 3 vs. 33 ± 3.7 ng/dl, P < 0.05). Plasma levels of corticosterone were 18% lower in animals fed DHA than in controls, but this difference was not statistically significant. Adrenal glomerulosa cells from DHA-fed rats produced less aldosterone in vitro in response to angiotensin II, ACTH, or potassium. The difference was less marked when aldosterone production was stimulated by supplying exogenous corticosterone, suggesting an effect of DHA on postreceptor steps in signal transduction or the early pathway of aldosteronogenesis. We found no significant differences in angiotensin receptor subtype, number, or affinity. Production of arachidonic epoxides by renal microsomes was 17% lower in DHA-fed animals than in controls (P < 0.05). Renal cortical mRNA levels of CYP4A genes and formation of 19-and 20-hydroxyeicosatetraenoic acid (HETE) did not differ between dietary groups. Plasma total cholesterol and high-density-lipoprotein (HDL) levels were significantly reduced in SHR fed the DHA supplement, but triglyceride levels were not significantly different. The effects of DHA on steroid and eicosanoid metabolism may be part of the mechanism by which this fatty acid prevents some of the hypertension in growing SHR.

Epoxy-Keto Derivative of Linoleic Acid Stimulates Aldosterone Secretion

“…Gamma-linolenic acid (C18:3, n-6) and docosahexaenoic acid (C22:6, n-3) have been shown to inhibit aldosterone production in hypertensive rats. 25,26 Although those inhibitory effects were originally attributed to the unmodified fatty acid, it is possible that oxidized products of the fatty acids were also active.…”

Nitric oxide enhancement and blood pressure decrease in patients with metabolic syndrome using soy protein or fish oil

“…A metaregression analysis of randomized trials verified that at doses between 3 and 5.6 g/d, fish oil reduced blood pressure in hypertensive individuals by up to 5.5/3.5 mmHg (14). The mechanisms implicated include blunting of the synthesis of rennin-angiotensin-aldosterone system by decreasing adrenal synthesis of aldosterone (33), changes in renal arachdonic metabolism (33), blunting the sympathetic activity in adrenal response to mental stress with reduced cortisol release (34), and reducing heart rate (35).…”

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

“…8 Alteration of the phospholipid profile in different organs may contribute to the antihypertensive effect of DHA. 32 There is a large body of evidence that demonstrates the role of the kidney in regulating blood pressure and the ability of oxidative stress to interfere with tubuloglomerular feedback.…”

“…5,6 Docosahexainoic acid (DHA), an -3 polyunsaturated fatty acid, has been reported to lower blood pressure (BP) and prevent the development of hypertension in experimental models as well as in humans. [7][8][9] DHA is also recognized as an activator of peroxisome proliferator-activated receptor (PPAR)-␣, which belongs to the nuclear hormone receptor superfamily and plays an important role in lipid metabolism. Apparently, PPAR␣ is implicated in metabolic disorders such as dyslipidemia, which is one of the risk factors of atherosclerosis.…”