Hypothalamic gene expression in ω-3 PUFA-deficient male rats before, and following, development of hypertension

Abstract

Dietary deficiency of ω-3 fatty acids (ω-3 DEF) produces hypertension in later life. This study examined the effect of ω-3 DEF on blood pressure and hypothalamic gene expression in young rats, before the development of hypertension, and in older rats following the onset of hypertension. Animals were fed experimental diets that were deficient in ω-3 fatty acids, sufficient in short-chain ω-3 fatty acids or sufficient in short- and long-chain ω-3 fatty acids, from the prenatal period until 10 or 36 weeks-of-age. There was no difference in blood pressure between groups at 10 weeks-of-age; however, at 36 weeks-of-age ω-3 DEF animals were hypertensive in relation to sufficient groups. At 10 weeks, expression of angiotensin-II(1A) receptors and dopamine D(3) receptors were significantly increased in the hypothalamic tissue of ω-3 DEF animals. In contrast, at 36 weeks, α(2a) and β(1) adrenergic receptor expression was significantly reduced in the ω-3 DEF group. Brain docosahexaenoic acid was significantly lower in ω-3 DEF group compared with sufficient groups. This study demonstrates that dietary ω-3 DEF causes changes both in the expression of key genes involved in central blood pressure regulation and in blood pressure. The data may indicate that hypertension resulting from ω-3 DEF is mediated by the central adrenergic system.

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

“…In light of this evidence, it is interesting that Begg et al 22 reported in this issue that the expression of angiotensin-II 1A receptors and dopamine D3 receptors was significantly increased in the hypothalamic tissue of o-3-deficient animals at age 10 weeks, and the a2a and b1 adrenergic receptor expression was significantly reduced at 36 weeks in animals that developed hypertension in adult life as a result of having received an o-3-deficient diet during the prenatal period. This model of hypertension, developed by Weisinger et al, formed the basis of many studies by the same group.…”

“…Begg et al 22 noted that at 10 weeks, the expression of angiotensin-II 1A receptors and dopamine D3 receptors significantly increased in the hypothalamic tissue, whereas at 36 weeks the a2a and b1 adrenergic receptor expression was significantly reduced in the o-3 DEF group. These alterations in the expression of angiotensin-II 1A , dopamine D3, a2a and b1 adrenergic receptors suggest that they may have a role in the pathobiology of hypertension, or they may simply be bystander changes.…”

“…22 It is not known whether these o-3 DEF animals develop the complications observed in humans with essential hypertension, such as malignant hypertension, hypertensive retinopathy, atherosclerosis, stroke, CHD, cardiac failure, cardiac arrhythmias and renal failure. A study in this direction is needed.…”

“…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.…”

“…These results also suggested that o-3 and o-6 fatty acids interact with each other to influence body weight, plasma leptin and, possibly, fatty acid composition and its metabolism in various tissues. It would have been interesting if the authors had studied hypothalamic Neuropeptide Y, serotonin, dopamine, pro-opiomelanocortin, melanocortins and acetylcholine levels in these studies, 22,25 to determine the cause for the changes in the consumption of food and water, lower body weight, less adiposity and lower plasma leptin levels. Unfortunately, in both studies, 22,25 the authors did not measure the fatty acid composition of the plasma, vascular tissue, kidneys, heart or liver to determine whether an o-3 PUFA deficiency was present in these tissues and in the brain.…”