Effects of the omega-3 fatty acids on vascular tone in hypercholesterolaemia and balloon arterial injury

Dietary polyunsaturated fatty acids (ω-3 PUFAs) are associated with reduced coronary heart disease (CHD) risk. To define mechanisms, we investigated the vasoactive properties of these fatty acids in a rat model of hypercholesterolaemia (HC) and balloon arterial injury. Mature Wistar Kyoto (WKY) rats were fed a control (C), HC-inducing diet or a HC diet after aortic balloon injury (HC+EI) for 3 weeks. Serum cholesterol (mg/dL) was increased in HC (793 ± 31) and HC + EI (857 ± 36) as compared to C (85 ± 3, p ≤ 0.001). Cumulative concentration-response curves to norepinephrine (NE, 10^-9 to 10^-5 mol/L) followed by docosahexaenoic (DHA) or eicosapentaenoic (EPA) (1 to 100 μmol/L) were generated in isolated aortic rings (intact and de-endothelialised, E-). Overall, contractions to NE (10^-9 to 10^-5 mol/L) in intact rings were diminished in HC and HC+EI groups than were apparent in the C group (p ≤ 0.001). De-endothelialised rings exhibited much greater NE contractile responses as compared to intact rings from each of the 3 groups. Endothelium-dependent relaxations to acetylcholine (10^-7 to 10^-4 mol/L) were significantly decreased in the HC+EI group. Relaxant responses to the ω-3 PUFAs, DHA and EPA (1-100 μmol/L) were similar in intact rings, but enhanced in E- rings among the 3 groups. De-endothelialised ring responses were -8.6 to -35.5% (C), -8.4 to -30.5% (HC), -7.8 to -25.6% (HC + EI) to DHA (1-100 μmol/L) and -6.8 to -33.9% (C), -4.8 to -40.8% (HC), -8.9 to -34.6% (HC + EI) to EPA (1-100 μmol/L). In areas of aortic intimal hyperplasia, lipid deposition quantified spectrophotometrically using oil red O (ORO) was greater in HC + EI (0.539 μmol ORO/mm² aortic tissue, p < 0.001) as compared to C (0.292) and HC (0.315) groups. We conclude that (1) aortic contractile properties to NE are altered in rats with HC and HC+EI, (2) dietary HC after aortic injury leads to intimal hyperplasia/lipid deposition and impaired endothelium-dependent relaxations in WKY rats, and (3) ω-3 PUFAs have vasorelaxant properties in HC and HC+EI rat aorta. These properties may be beneficial in CHD.