Essential fatty acids and their metabolites in the context of hypertension

Abstract

H ypertension is associated with an increase in peripheral vascular resistance, insulin resistance, endothelial dysfunction and enhanced activity of the sympathetic nervous system. 1 The condition causes morbidity and mortality. Hence, understanding its pathobiology is necessary to develop effective strategies for both prevention and management.There is increasing evidence that nutritional factors and type and level of fat in the diet are critical in the pathogenesis of essential hypertension. 2 Earlier, Weisinger et al. 3 showed that perinatal deficiency of the essential dietary o-3 fatty acid a-linolenic acid (ALA) resulted in a reduction in hypothalamic docosahexaenoic acid (DHA,. This caused hypertension in Sprague-Dawley rats, although hypothalamic DHA levels eventually returned to normal in the adults. This suggests that restoring hypothalamic DHA to normal is not sufficient to prevent the development of hypertension. Li et al. 4 reported that in animals fed a diet rich in o-6 with very little ALA and then re-fed the control diet rich in ALA for 24 weeks, DHA levels were still significantly less than the control values in phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol fractions (by 9, 18 and 34%, respectively). The results led to the suggestion that o-6/o-3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with dysfunction or down-regulation of the conversion of ALA to DHA. In this issue of the journal, Begg et al. 5 report that different sources of ALA (canola or flaxseed oil) are effective in preventing hypertension related to o-3 fatty acid deficiency. However, animals that received canola oil had lower body weight, less adiposity, lower plasma leptin levels and consumed less food, whereas animals fed safflower oil + flaxseed oil also had lower but less marked reductions in adiposity and plasma leptin levels compared with animals that were given safflower oil only. This latter group developed an o-fatty acid deficiency. In addition, safflower oil + flaxseed oil-fed animals consumed more food and water. These results suggest that body weight, plasma leptin and brain DHA are the main determinants of blood pressure. This study also implies that there exists an interaction between o-3 and o-6 fatty acids that influences body weight, plasma leptin and, possibly, fatty acid composition and its metabolism in various tissues. This potential mechanism was not investigated by Begg et al. 5 and may have a function in the pathophysiology of hypertension and metabolic syndrome. 6 Earlier, we observed that in patients with uncontrolled essential hypertension, O 2 À. , hydrogen peroxide and lipid peroxides were produced in significantly large amounts by both unstimulated and stimulated polymorphonuclear leukocytes that reverted to normal after the control of hypertension by anti-hypertensive medicines such as calcium antagonists, b blockers and ACE inhibi...

Lipoxins, resolvins, protectins, maresins and nitrolipids, and their clinical implications with specific reference to diabetes mellitus and other diseases: part II

“…Similar to their beneficial action in STZ-induced Type 1 DM and diet-induced Type 2 DM, LXs, Rvs, protectins and nitrolipids are likely to be useful in the prevention and management of other inflammatory conditions, such as lupus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, diabetic retinopathy and age-related macular degeneration [37,124,135,[140][141][142][143][144][145][146][147][148][149][150][151][152]. It is likely that all diseases in which low-grade systemic inflammation play a significant role, such as obesity, nonalcoholic fatty liver disease, hypertension, atherosclerosis, hyperlipidemia, CHD, depression, schizophrenia, Alzheimer's disease, aging, osteoporosis, Huntington's disease, polycystic ovarian syndrome, dermatitis, psoriasis, glomerulonephritis of different etiologies, scleroderma and other collagen vascular diseases may be due to deficiency of cyto protective LXs, Rvs, protectins, MaRs and nitrolipids [37,124,136,[141][142][143][144][145][146][147][148][149][150][151][152].…”

“…It is likely that all diseases in which low-grade systemic inflammation play a significant role, such as obesity, nonalcoholic fatty liver disease, hypertension, atherosclerosis, hyperlipidemia, CHD, depression, schizophrenia, Alzheimer's disease, aging, osteoporosis, Huntington's disease, polycystic ovarian syndrome, dermatitis, psoriasis, glomerulonephritis of different etiologies, scleroderma and other collagen vascular diseases may be due to deficiency of cyto protective LXs, Rvs, protectins, MaRs and nitrolipids [37,124,136,[141][142][143][144][145][146][147][148][149][150][151][152]. It is suggested that in conditions such as hypertension, schizophrenia, depression, Alzheimer's disease and Huntington's disease, PUFAs, LXs, Rvs, protectins and MaRs may act not only on peripheral tissues, but also on specific areas of the brain, such as the hypothalamus.…”

Is aortic aneurysm preventable?

“…Previously, we showed that PUFAs and their metabolites play a critical role in the pathobiology of hypertension, pre-eclampsia, type 2 diabetes mellitus and metabolic syndrome [14,17,18,[22][23][24][25][26][27][28][29][30][31][32][33][34] . We, previously showed that AA prevents chemical-induced type 1 and type 2 diabetes, partly, due to its conversion to anti-inflammatory LXA4, [17,18] implying that the precursor PUFAs need to be converted to their specific anti-inflammatory metabolites to produce their beneficial actions.…”

Pre(peri)-natal ω-3 PUFA deficiency-induced hypertension and its broader implications

“…2 -, H 2 O 2 , lipid peroxides, NADPH oxidase, ACE activity, and myeloperoxidase activity, and decreased half-life and/or concentrations of PGI 2 and endothelial nitric oxide. 2,12 It is worthwhile to investigate whether these abnormalities are present in the o-3-deficient hypertension model of Begg et al 22 Low-grade systemic inflammation, as evidenced by enhanced plasma levels of interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and high-sensitive CRP (hs-CRP), occurs in patients with hypertension. [34][35][36][37][38] Begg et al 22 have not measured plasma cytokines and hs-CRP levels in the o-3-deficient hypertensive animal model to know whether low-grade systemic inflammation is present.…”

“…This is especially true in the light of the fact that increases in peripheral vascular resistance, insulin resistance and endothelial dysfunction and enhanced activity of the sympathetic nervous system are observed in obesity, type 2 diabetes mellitus and hypertension. [2][3][4][5][6][7][8][9][10][11] Hypertension is characterized by an increase in peripheral vascular resistance that could be attributed to the loss or decrease in endothelium-dependent vasodilation. The endothelium produces vasoactive factors such as prostacyclin (PGI 2 ), nitric oxide (NO), endothelium-derived hyperpolarizing factor, endothelin and prostaglandin E 1 (PGE 1 ).…”