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Plasma Free Fatty Acids and Endothelium-Dependent Vasodilation: Effect of Chain-Length and Cyclooxygenase Inhibition

Departments of Clinical and Experimental Medicine and Internal Medicine, University of Padova, 35100 Padova, Italy

Address all correspondence and requests for reprints to: Angelo Avogaro, M.D., Cattedra di Malattie del Metabolismo, Via Giustiniani 2, 35100 Padova, Italy. E-mail: avogaro{at}ux1.unipd.it

Free fatty acids (FFA) are known to interfere with glucose metabolism. Moreover, it has been shown that they are able to impair the endothelium-dependent vasodilation. Therefore, we sought to determine whether their negative effect on endothelial function depends on their chain length or on their ability to modify PG production.

Fourteen normal volunteers were studied under baseline conditions and then randomly allocated to two of the following four studies: 1) long chain triglyceride (LCT) emulsion and heparin infusion (n = 7), 2) infusion of an emulsion containing 56% medium chain triglycerides (MCT) and 44% LCT plus heparin (n = 7), 3) infusion of LCT and heparin preceded by an iv bolus of 900 mg lysine-salycilate (ASA; n = 7), and 4) after an iv bolus of ASA (n = 7). Basal forearm blood flow (FBF), endothelium-dependent vasodilation in response to intraarterial acetylcholine (Ach), and endothelium-independent vasodilation in response to intraarterial nitroprusside were assessed by venous occlusion plethysmography. Both LCT and MCT infusions significantly increased basal FBF from 1.58 ± 0.35 to 2.60 ± 0.76 and 2.28 ± 0.56 mL/min·100 mL tissue, respectively (both P < 0.05). This increase was also observed for LCT plus heparin, but not after ASA alone. The percent increase in FBF during Ach was lowered during both LCT (252 ± 34% of the ratio infused/control arm at maximal Ach dose) and MCT (255 ± 41%) compared to the baseline conditions (436 ± 44%; both P < 0.05). The response to Ach was also lower during LCT plus ASA, whereas it was similar to baseline with ASA alone. No differences were observed in the response to nitroprusside among the experimental conditions.

In conclusion, 1) the effect of FFA on endothelium-dependent vasodilation is independent of their chain length; 2) both LCT and MCT increase baseline FBF, independently from cyclooxygenase inhibition; and 3) acute ASA administration does not affect endothelium-dependent vasodilation. The FFA effect on the endothelial response to Ach may contribute to altered endothelial function and, hence, to the development and progression of atherosclerotic cardiovascular disease.

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