Differential effects of dietary fish oil on myocardial prostaglandin I2 and thromboxane A2 production
Abeywardena, M.Y. | McLennan, P.L. | Charnock, J.S.
Marmoset monkeys (Callithrix jacchus) were maintained for 24 mo on a standard primate diet [reference (Ref) diet] or this diet supplemented (8% wt/wt) with either sheep fat (SF), sunflower seed oil (SSO), or tuna fish oil (TFO). The polyunsaturated fatty acids (PUFA) of myocardial phospholipids demonstrated significant alterations as a result of the dietary (n-3) or (n-6) lipid supplementation. The reduction (P < 0.05) in prostaglandin (PG) I2 in PUFA diet-fed groups (SSO, 113.8 +/- 7.8; TFO, 87.9 +/- 8.2 compared with Ref, 153.9 +/- 7.4 pg/mg dry wt) seems to be due to the rate limitation of the endogenous substrate, because the addition of exogenous arachidonic acid (AA) has obliterated the dietary difference. However, AA did not increase the basal PGI2 production in the Ref or SF dietary groups, which differed from that for thromboxane (Tx) A2 where 2- to 5-fold stimulation was observed. It is suggested that there exists a preferential channeling mechanism to direct AA derived from phospholipase hydrolysis of membrane phospholipids toward PGI2 synthesis. Conversely, the bulk of the AA for TxA2 biosynthesis appears to be supplied by a cytosolic nonesterified fatty acid pool. The effective replacement of AA of this pool and a specific inhibition of TxA2 synthetase enzyme complex by the (n-3) PUFA of fish oil are offered as likely mechanisms (or the greater inhibition of TxA2 compared with PGI2 production observed in the present and previous studies. The present data on myocardial eicosanoids correlate well with the beneficial qualities of (n-3) and (n-6) dietary PUFA on cardiac function that we have reported previously.
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