PHARMACOLOGY OF OMEGA-3 FATTY ACIDS IN MAN

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The potential health benefits of omega-3 fatty acids from marine oils are being intensively investigated and some of the most promising areas are those of ameliorating vascular disease and lowing blood pressure. Many of the effect of omega-3 fatty acids have been attributed to changes in eicosanoid production, but few studies in man have measured the in vivo synthesis of these substances and related fish oil-induced alterations to functional ones. While lowering blood pressure, omega-3 FA reduce vasoconstrictor/proaggregatory thromboxane synthesis in man and spare or even increase that of vasodilator/anti-aggregatory prostacyclin. Their effects on the production of prostagladin E2 and other eicosanoids important in renal function and vascular tone are not defined in man and no studies on omega-3 effects in subjects with known sodium balance, renin or volume status have been performed. Recently, it has been noted that treating hypertension with beta-blockers and diuretics has not yielded as great a reduction in cardiac risk as predicted. This may be due to unfavorable effects of these drugs in elevating plasma VLDL and lowering HDL. Omega-3 fatty acids, however, have been found to have the opposite effects on plasma lipids while lowering blood pressure, so they have the potential for being useful adjunctive therapy in treated hypertension. The proposed research will define the dose-response relationship in the hypotensive actions of omega-3 fatty acids and assess their effect on hypertension in blacks and women. Alteration in the endogenous synthesis of prostaglandins, thromboxanes and novel epoxides during omega-3 ingestion will be measured with stat-of-the-art GC/MS methods and correlated with changes in blood pressure, vascular capacitance and resistance, as well as in angiotensin modulation and electrolyte excretion in well-defined subjects. The effects on plasma lipid changes due to anti-hypertensive drugs in more severely hypertensive patients will also be studied. This integrated and focussed approach will define which hypertensives might benefit or be worsened by omega-3 fatty acid supplements and the mechanisms by which this would occur.