Dietary n-3 fatty acids alter angiotensin-induced contraction and 1,2-diacylglycerol fatty acid composition in thoracic aortas from diabetic rats

Abstract

The effect of diabetes on the incorporation of long-chain n-3 fatty acids into thoracic aorta smooth muscle phospholipids and 1,2-diacylglycerol, and on the contractile response of aortic rings to angiotensin II, was examined in streptozotocin-induced diabetic rats. In diabetic animals fed a diet containing 1% of fatty acids as n-3 fatty acids, smooth muscle membrane levels of 18:2n-6 were elevated in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, whereas 20:4n-6 was depleted. The resultant decreased ratios of 20:3/18:2 and 20:4/20:3 indicate inhibition of delta6- and delta5-desaturase activity in the diabetic state. A diet containing 5% of fatty acids as n-3 fatty acids increased phospholipid levels of eicospentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) several-fold, but with a further reduction in 20:4n-6. Similarly, 1,2-diacylglycerol from rats fed the high n-3 diet was enriched in EPA, DPA and DHA. When incubated with 10(-8) M angiotensin II, the contractile response of intact aortic rings from diabetic animals fed the high n-3 diet was only 60.8+/-9.3% that of controls fed the same diet. However, contractile response was not significantly different from control animals fed the low n-3 diet (55.6+/-7.9%). The results indicate that vascular smooth muscle phospholipid n-6 and n-3 fatty acid metabolism is altered in diabetes, resulting in changes to the fatty acid profile of 1,2-diacylglycerol. Moreover, elevating membrane phospholipid and 1,2-diacylglycerol content of EPA, DPA and DHA partially ameliorates the depressed response to angiotensin II seen in the diabetic state.