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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL035380-06
Application #
3349212
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1991-01-01
Project End
1992-11-30
Budget Start
1991-01-21
Budget End
1992-11-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
van Sorge, Nina M; Cole, Jason N; Kuipers, Kirsten et al. (2014) The classical lancefield antigen of group a Streptococcus is a virulence determinant with implications for vaccine design. Cell Host Microbe 15:729-740
Knapp, H R; Murray, J J (1994) Leukotrienes as mediators of nasal inflammation. Adv Prostaglandin Thromboxane Leukot Res 22:279-88
Knapp, H R; Sladek, K; Fitzgerald, G A (1992) Increased excretion of leukotriene E4 during aspirin-induced asthma. J Lab Clin Med 119:48-51
Braden, G A; Knapp, H R; FitzGerald, G A (1991) Suppression of eicosanoid biosynthesis during coronary angioplasty by fish oil and aspirin. Circulation 84:679-85
Knapp, H R; Miller, A J; Lawson, J A (1991) Urinary excretion of diols derived from eicosapentaenoic acid during n-3 fatty acid ingestion by man. Prostaglandins 42:47-54
Knapp, H R (1991) Hypotensive effects of omega 3 fatty acids: mechanistic aspects. World Rev Nutr Diet 66:313-28
Greene, H L; Swift, L L; Knapp, H R (1991) Hyperlipidemia and fatty acid composition in patients treated for type IA glycogen storage disease. J Pediatr 119:398-403
Knapp, H R (1990) Polyunsaturates, endogenous eicosanoids, and cardiovascular disease. J Am Coll Nutr 9:344-51
Knapp, H R (1990) Reduced allergen-induced nasal congestion and leukotriene synthesis with an orally active 5-lipoxygenase inhibitor. N Engl J Med 323:1745-8
Knapp, H R (1990) Prostaglandins in human semen during fish oil ingestion: evidence for in vivo cyclooxygenase inhibition and appearance of novel trienoic compounds. Prostaglandins 39:407-23

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