Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension

Abstract

Patients with uncontrolled essential hypertension have elevated concentrations of superoxide anion (O 2 ÀK ), hydrogen peroxide (H 2 O 2 ), lipid peroxides, endothelin, and transforming growth factor-b (TGF-b) with a simultaneous decrease in endothelial nitric oxide (eNO), superoxide dismutase (SOD), vitamin E, and long-chain polyunsaturated fatty acids (LCPUFAs). Physiological concentrations of angiotensin II activate NAD(P)H oxidase and trigger free radical generation (especially that of O 2 ÀK ). Normally, angiotensin II-induced oxidative stress is abrogated by adequate production and release of eNO, which quenches O 2 ÀK to restore normotension. Angiotensin II also stimulates the production of endothelin and TGF-b. TGF-b enhances NO generation, which in turn suppresses TGF-b production. Thus, NO has a regulatory role on TGF-b production and is also a physiological antagonist of endothelin. Antihypertensive drugs suppress the production of O 2 ÀK and TGF-b and enhance eNO synthesis to bring about their beneficial actions. LCPUFAs suppress angiotensin-converting enzyme (ACE) activity, reduce angiotensin II formation, enhance eNO generation, and suppress TGF-b expression. Perinatal supplementation of LCPUFAs decreases insulin resistance and prevents the development of hypertension in adult life, whereas deficiency of LCPUFAs in the perinatal period results in raised blood pressure later in life. Patients with essential hypertension have low concentrations of various LCPUFAs in their plasma phospholipid fraction. Based on this, it is proposed that LCPUFAs serve as endogenous regulators of ACE activity, O 2 ÀK , eNO generation, and TGF-b expression. Further, LCPUFAs have actions similar to statins, inhibit (especially o-3 fatty acids) cyclooxygenase activity and suppress the synthesis of proinflammatory cytokines, and activate the parasympathetic nervous system, all actions that reduce the risk of major vascular events. Hence, it is proposed that availability of adequate amounts of LCPUFAs during the critical periods of growth prevents the development of hypertension in adulthood.

Plasma Polyunsaturated Fatty Acids and the Decline of Renal Function

“…PUFAs may reduce inflammation through several possible pathways, such as reduction of nitric oxide (24 ), downregulation of TNF-␣ (25 ), and modulation of protein kinases (26 ).…”

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

“…Depletion of n-3 PUFAs in hepatic steatosis may result from dietary causes or inhibition of hepatic desaturases as a result of excessive exposure to ROS and subsequent lipid peroxidation (Das, 2004). Essential fatty acids, such as linoleic acid (18:2, n-6) and linolenic acid (18:3, n-3) are precursors of n-3 and n-6 PUFAs and therefore must be obtained from diets.…”

Omega-3 Fatty Acids and Age-Related Diseases: Realities and Prospects

“…Этот эффект может быть связан с изменением внутри-клеточного сигнала трансдукции, изменением степени вязкости плазмы крови или влиянием на активность ан-гиотензин-превращающего фермента (АПФ [7]. Таким образом, суммируя эффекты, которые ока-зывают ω-3 ПНЖК на показатели АД, можно выделить следующие: 1.…”