Nonesterified fatty acids and endothelial dysfunction

Nonesterified fatty acids (NEFA) induce vascular effects, such as the inhibition of insulin-induced nitric oxide (NO) production. In small arteries, relaxation is largely NO-independent. We aimed to assess the effect of elevated NEFA on NO-independent vasodilation. Protocols were performed before and after 120 min of a lipid emulsion infusion. We performed: (1) the flow-induced dilatation of the brachial artery (NO-dependent), (2) intrabrachial bradykinin (BK) infusion before and after inhibition of prostaglandins (PG) and NO and (3) intraarterial infusion of ouabain, a Na+/K+ ATPase blocker, alone or in combination with BaCl2, a potassium channel blocker. No changes in flow-mediated vasodilation were induced by elevated NEFA. After the inhibition of PG and NO, BK increased forearm blood flow (FBF) similarly, indicating that the increase in FBF is not dependent on NO and PG production. However, elevated NEFA blunt FBF on both occasions. Coinfusion of ouabain with BaCl2 caused a significant decline in FBF in baseline condition (- 48 +/- 5%, p < 0.01). This effect on FBF was blunted at high NEFA ( - 28 +/- 2%, p < 0.01 vs. baseline condition). In conclusion, elevated NEFA do not impair NO-dependent vasodilation; this effect appears to be mediated by a reduced potassium-mediated vasodilation. This makes more Rely their negative action on metabolism and haemodynamic coupling. (C) 2002 Elsevier Science B.V. All rights reserved.