Current Vascular Pharmacology, 2009, 7, 000-000 1 1570-1611/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd. Omega-3 Polyunsaturated Fatty Acids: Their Potential Role in Blood Pres- sure Prevention and Management Arrigo F.G. Cicero a,* , Sibel Ertek b and Claudio Borghi a a Hypertension Research Unit , Internal Medicine, Aging and Kidney Diseases Department, Alma Mater Studiorum Uni- versity of Bologna, Bologna, Italy; b Endocrinology and Metabolic Diseases Department, Ufuk University Medical Fac- ulty, Dr. Ridvan Ege Hospital, Ankara-Turkey Abstract: Omega-3 ( -3) polyunsaturated fatty acids (PUFAs) from fish and fish oils appear to protect against coronary heart disease: their dietary intake is in fact inversely associated with cardiovascular disease morbidity/mortality in popula- tion studies. Recent evidence suggests that at least a part of this protective effect is mediated by a relatively small but sig- nificant decrease in blood pressure (BP) level. In fact, -3 PUFAs exhibit wide-ranging biological actions that include regulating both vasomotor tone and renal sodium excretion, partly competing with -6 PUFAs for common metabolic en- zymes and thereby decreasing the production of vasoconstrictor rather than vasodilator and anti-inflammatory eicosa- noids. PUFAs also reduce angiotensin-converting enzyme (ACE) activity, angiotensin II formation, Tumor Growth Fac- tor-beta (TGF- ) expression, enhance endothelial nitric oxide (NO) generation and activate the parasympathetic nervous system. The final results are improved vasodilation and arterial compliance of both small and large arteries. Preliminary clinical trials involving normotensive and hypertensive dyslipidaemic patients, diabetics and elderly subjects, confirm this working hypothesis: 3 meta-analyses suggest that PUFAs are able to slightly, but significantly improve arterial hyperten- sion. Future research will clarify if PUFA supplementation could improve the antihypertensive action of specific BP low- ering drug classes and of statins. Keywords: Fish oil, omega 3 fatty acids, polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid, blood pres- sure, hypertension, PUFA. INTRODUCTION The inverse association between -3 PUFA intake and cardiovascular disease morbidity/mortality was established following the observation that the Greenland Inuit had low mortality from coronary heart disease (CHD) despite a fat- rich diet. In the 1970s, the Danish investigators Bang and Dyerberg proposed that this could be because of the -3 PUFA high content in the Inuit diet, which consisted largely of fish, seal and whale [1]. In fact, in these subjects plasma -3 PUFA concentrations are highly correlated with dietary PUFAs and inversely correlated with diastolic BP [2]. From that preliminary evidences, a large number of studies evalu- ated the potential beneficial effects of -3 PUFAs in in- flammatory, autoimmune, renal and cardiovascular diseases [3, 4]. The most interesting data regard heart disease, either secondary to arrhythmias or atherosclerosis [5-7]. In particular, the inverse association between PUFA in- take and stroke incidence observed in different longitudinal epidemiological studies [8, 9], even reflected in a slower age-related cognitive decline [10] support the hypothesis that PUFAs could play a significant role in also modulating the main stroke independent risk factor, that is arterial hyperten- sion. However other authors suggest that the observed in- verse relationship between PUFA consumption and stroke incidence is the consequence of the atrial fibrillation preven- tive action of PUFAs [11]. *Address correspondence to this author at the Internal Medicine, Aging and Kidney Diseases Dept., Sant'Orsola-Malpighi Hospital - University of Bo- logna, Via Massarenti, 9 - 40138 Bologna H Italy; Tel. +39-0516364920 Fax +39-051391320; E-mail: afgcicero@cardionet.it Compared with traditional diets, PUFA intake in indus- trialized countries has markedly shifted during the past 150 years toward higher amounts of -6 PUFAs and lower amounts of -3 PUFAs, with a parallel increase in CHD incidence [12]. However, the inverse correlation between PUFAs intake and BP may not be true for each ethnicity [13]. Beyond their well-known antiarrhythmic effect and triglycerides lowering action [11], -3 PUFAs also have a small but significant BP lowering effect that from an epide- miological point of view could have a relevant impact on cardiovascular disease prevention. The aim of this review is to critically evaluate the avail- able information about the effect of PUFA on BP control and prevention of hypertension development. DATA SOURCES AND SELECTION CRITERIA We searched PubMed and EMBASE for relevant articles by using the key words IfishJ, Ifish oilsJ, Iomega 3 fatty acidsJ, Ipolyunsaturated fatty acidsJ, IPUFAJ, IEicosapen- taenoic acidJ, IEPAJ, IDocosahexaenoic acidJ, IDHAJ and Iblood pressureJ or Iarterial hypertensionJ, using a com- bined text word and MESH heading search strategy. Then we cross-matched references with those found in each paper and we cited the most representative ones. BIOCHEMICAL CLASSIFICATION AND FOOD SOURCES Alpha-linolenic acid (ALA; 18:3 -3) and linoleic acid (LA; 18:2 -6) are essential fatty acids for humans [14]. LA