Dietary n-3 fatty acids alter the contractile response to thromboxane A2 agonists of porcine coronary arteries

Dietary supplementation with marine fish oils rich in n-3 fatty acids reduces circulating thromboxane A2 (TxA2). However, the effects on thomboxane A2 receptor mediated vascular reactivity are uncertain. The aim of this study was to test the hypothesis that dietary modification of TxA2 levels alters vascular responsiveness to TxA2 analogues. Juvenile female white pigs were fed a diet enriched in either 5% (w/w) fish oil or beef tallow for 6 weeks. Serum and myocardial tissue levels of eicosapentaenoic and docosahexaenoic acid reached a plateau during this period. Vascular responses were measured in isolated coronary arterial rings with intact endothelium by isometric tension measurement. Arteries from pigs fed fish oil produced a greater maximum vasoconstrictor tension to the TxA2 analogue U46619 than did rings from pigs fed beef tallow (120 ± 6% compared to 92 ± 8%, values represented as a percentage relative to the maximum vasoconstrictor effect obtained to KCl, regression analysis, analysis of variance, P ≤ 0.05). The vasoconstrictor potency of U46619 was similar in both treatment groups. The vasoconstrictor EC50 was 10.3 (6.8–15.7) nmol/L (mean, 95% confidence interval) for fish oil and 9.5 (5.7–15.8) nmol/L for beef tallow treated animals. Changes in vascular responses to U46619 were associated with a fourfold difference in plasma thromboxane B2 levels between treatment groups (12.1 ± 2.6 pg/mL fish oil, 48.3 ± 3.1 pg/mL beef tallow, Students’ unpaired t-test P ≤ 0.05). Vasoconstrictor responses obtained to endothelin-1, KCl and 5-hydroxtryptamine and the vasodilator response to sodium nitroprusside were not different between treatment groups. Dietary manipulation of thromboxane A2 levels by n-3 fatty acids alters vascular reactivity to U46619, possibly as a result of agonist-induced desensitization of thromboxane A2 receptors.