The Anti-hypertensive Actions Exerted By Dietary Omega-3 Polyunsaturated Fatty Acid In Chinese And Its Mechanism

Background:Essential hypertension (EH) is a state of systemic metabolic disorder caused by interaction between genetic background in humans and environmental factors. Abnormal activation in the signaling pathway composed of rennin-angiotensin system (RAS) and downstream mitogen-activated protein kinase (MAPK) has been closely related to the occurrence and prognosis of EH. All existing evidence has shown that increased consumption of dietary n-3 polynusaturated fatty acid (PUFA) can notablely reduce systolic blood pressure (SBP) and diastolic BP (DBP) in western hypertensive patients, but no randomized clinical trial (RCT) was conducted in China. Thus, whether dietary n-3 PUFAhas a hypotensive activity in Chinese populations by downregulating the RAS-MAPK signaling pathway is presently unclear.Aim and Methods:The objective of the present study was to investigate if dietary n-3 PUFA can exert anti-hypertensive effect in Chinese EH patients and its possible mechanism by using the research methods as below:(1) Meta-analyses were performed to examine the association of food n-3 PUFA and its biomarker with hypertension and other chronic diseases;(2) A cross-sectional study was performed to investigate the association between serum n-3 PUFA as biomarker of dietary intake and the prevalence of hypertension in Chinese populations;(3) A case-control study using metabolomics data processing methods was performed to identify the potential FA biomarker in distinguishing between hypertensive patients and normotensive individuals;(4) A randomized clinical trial (RCT) was conducted to investigate the effects of dietary n-3 PUFA on BP and other cardio-metabolic risk factors in Chinese hypertensive individuals;(5) An animal experiment was performed to investigate the effects of dietary n-3 PUFA on RAS-MAPK signaling pathway in spontaneously hypertensive rats (SHR).Results:Meta-analyses show that high intake of long-chain (LC) n-3 PUFA was significantly associated with 27% reduction of EH risk, serum LC n-3 PUFA as biomarker was negatively associated with risk of ischemic stroke and colorectal cancer, and increased intake of n-3/n-6 PUFA ratio was significantly associated with risk of breaset cancer in females. In the cross-sectional study, after adjustment for lifestyle factos including age, gender, BMI, smoking, drinking, physicial activity, and salt intake as well as clinical parameters including heart rate, blood lipids and fasting glucose levels, high serum composition of 16:0,16:ln-7 and â–³6-desaturase index (18:3n-6/18:2n-6) as well as low 22:6n-3 and â–³5-desaturase index (20:4n-6/20:3n-6) were significantly associated with a low prevalence of hypertension. In case-control study, serum FA profile in hypertensive patients was typically characterized by higher 16:0 and 16:ln-7, and lower 18:2n-6 and 22:6n-3 compared with normotensive controls; 22:6n-3 and 16:ln-7 were identified as the important FA contributing most to the intergroup separations; after adjustment for lifestyle factors and clinical paramaters, newly diagnosed hypertension was negatively associated with 22:6n-3, but positively associated with 16:ln-7. In RCT of Chinese EH patients intervened by fish oil (FO), flaxseed oil (ALA) and corn oil (CO), FO supplements for 90 days can significantly reduce DBP, high-sensitivity C-reactive protein (hs-CRP), and insulin resistence index (I SI) compared with baseline data within group; plasma homocysteine, serum total colestoral (TC) and LDL-C levels were significantly reduced in FO group, and a significant difference in net change was found between FO and CO groups. In animal experiment by different dietary fat intervention, long-chain (LC) n-3 PUFA supplement for 6 weeks can significantly reduce SBP, heart rate (HR), serum concentrations of total colestoral (TC), plasma concentrations of Angâ…¡ and ratio of Ang â…¡/Ang (1-7), down-regulate the aortic tissue expression of ACE mRNA, p-Erk and p-38 MAPK as well as up-regulate Mas receptor mRNA expression in SHR.Conclusion:Serum proportion of LC n-3 PUFA was associated with a lower risk of EH, and increased consumption of LC n-3 PUFA can reduced diastolic BP, TC and LCL-C in Chinese hypertensive patients, which may be related to the RAS-MAPK signaling pathway down-regulated by 22:6n-3. Present fingdings added further evidence that LC n-3 PUFA can potentially exert the hypotensive effects and improve glucose and lipidmetabolism in Chinese EH patients. More RCTs of dietary n-3 PUFA on blood pressure are warranted in China.