Dietary n-3 fatty acids alter the contractile response to thromboxane A 2 agonists of porcine coronary arteries

Abstract

Dietary supplementation with marine fish oils rich in n-3 fatty acids reduces circulating thromboxane A 2 (TxA 2). However, the effects on thomboxane A 2 receptor mediated vascular reactivity are uncertain. The aim of this study was to test the hypothesis that dietary modification of TxA 2 levels alters vascular responsiveness to TxA 2 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 TxA 2 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 EC 50 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 B 2 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 A 2 levels by n-3 fatty acids alters vascular reactivity to U46619, possibly as a result of agonist-induced desensitization of thromboxane A 2 receptors.