Eicosapentaenoic acid [20 : 5 (n-3)] is not oxidized by the purified cyclooxygenase from sheep vesicular glands in the conditions of low peroxide tone in which arachidonate [20 : 4 (n-6)] is rapidly oxygenated. When the level of peroxide in incubation mixtures is allowed to rise, there is a dramatic change in reactivity of the cyclooxygenase to react with 20 : 5 (n-3) at one-halt the rate and one-third the extent observed with 20 : 4 (n-6). Overall, the low peroxide levels expected in vivo would most probably cause the (n-3) type of fatty acid to be a general inhibitor of prostaglandin formation, through both reversible and irreversible actions at the enzyme site.

The effect of altering the abundance of precursors and inhibitors of prostaglandin formation by dietary supplements of fish oil was investigated in dogs with experimentally induced myocardial infarction. Prior to induction, 10 male mongrel dogs were fed standard dog chow supplemented with 25% of the total calories as menhaden oil for 36 to 45 days. The fatty acid composition of th lipids in plasma and platelets changed to reflect the increased intake of polyunsaturated fatty acids of the n-3 type. Thrombosis and subsequent infarction was induced by electrical stimulation of the left circumflex coronary artery of ambulatory dogs that were monitored by telemetry. Upon stimulation of control animals, the frequency of ectopic beats rose from less than 10% at the beginning to about 80% after 19 hours. In contrast, the oil-fed dogs maintained a more normal ECG pattern, showing less than 30% ectopic beats after 19 hours. In these animals, the size of infarction (measured by formazan formation) was 3% of the left ventricle compared to 25% in the control animals. The results suggest that dietary supplementation with fish oil may be beneficial in reducing myocardial damage associated with coronary artery thrombosis.

The protective effect of the (n-3) fatty acids in menhaden fish oil on acute cerebral ischemia was investigated in cats. Cerebral ischemia was produced by ligation of the left middle cerebral artery of cats fed either a basal diet of feline cat chow or the basal diet supplemented with 8% of the calories as menhaden oil for 18-24 days. Fatty acids esters of 20:5 (n-3) were increased and the 18:2 (n-6) decreased in the heart and liver of cats fed supplemental fish oil, but the brain lipid showed no effect of the diet. We found that the neurological deficit and the volume of brain infarction in the group treated with fish oil was less than that of the control group. The present findings suggest that moderate dietary supplements of fish oil may be beneficial in the prophylactic treatment of ischemic cerebral vascular disease.

Epidemiologic studies suggest that high dietary intake of eicosapentaenoic acid (EPA), a precursor of the trienoic prostaglandins, is associated with a low incidence and reduced extent of myocardial infarction. Vascular reactivity of isolated aortic strips from rats maintained for 3 weeks on a control diet or on a diet supplemented with menhaden fish oil (17% EPA) was examined with norepinephrine, sodium arachidonate, KC1, PGF2 alpha and nitroprusside. Aortic strips from rats fed the fish oil diet were significantly less responsive to the contractile effects of norepinephrine and arachidonate compared to those from control diet rats. Treatment of aortic strips with indomethacin decreased responsiveness to norepinephrine. The magnitude of the decrease was greater in control rats resulting in a similar vascular response between the 2 groups after blockade. Contractions to arachidonate were abolished by indomethacin. There were no differences in vascular responses to KC1, PGF2 alpha and nitroprusside in aortic strips from control diet rats and those from the fish oil diet rats. Aortic strips from the fish oil diet rats contained more EPA than those from the control diet rats. Thus, the contractile effect of norepinephrine in isolated rat aortic strips is normally augmented by intrinsic prostaglandins, and this augmentation is diminished by dietary intake of EPA.

Study of the viscoelastic properties of the arterial tree in man i s d i f f i c u l t. Pbst previous reports on a r t e r i a l canpliance (d i s t e n s i b i l i t y) in man, i n which canpliance has been estimated d i r e c t l y fran pressure-volme relationships, have involved arteries taken f r m cadavers, (1 , 2). In vlvo studies in hmans have usually u t i l i z e d indirect estimates of m p l i a n c e (3-8), such as a r t e r i a l pulse wave velocity (5,B). Arterial canpliance has been a sanewhat neglected subject i n recent cardiovascular research: t h i s probably r e f l e c t s methalological d i f f i c u l t i e s rather than lack of interest (3-7) and does not imply t h a t aberrations i n a r t e r i a l distens i b i l i t y play no i m p r t a n t role i n human circulatory pathophysiology and disease.