de Kreutzenberg S V, Crepaldi C, Marchetto S, Calò L, Tiengo A, Del Prato S, Avogaro A
Department of Clinical and Experimental Medicine, University of Padova, Italy.
J Clin Endocrinol Metab. 2000 Feb;85(2):793-8. doi: 10.1210/jcem.85.2.6352.
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 i.v. bolus of 900 mg lysine-salicylate (ASA; n = 7), and 4) after an i.v. 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.
已知游离脂肪酸（FFA）会干扰葡萄糖代谢。此外，已有研究表明它们能够损害内皮依赖性血管舒张功能。因此，我们试图确定它们对内皮功能的负面影响是取决于其链长还是其改变前列腺素（PG）生成的能力。对14名正常志愿者在基线条件下进行研究，然后将他们随机分配到以下四项研究中的两项：1）长链甘油三酯（LCT）乳剂和肝素输注（n = 7），2）输注含56%中链甘油三酯（MCT）和44%LCT的乳剂加肝素（n = 7），3）静脉推注900 mg赖氨酸 - 水杨酸盐（阿司匹林；ASA）后输注LCT和肝素（n = 7），4）静脉推注ASA后（n = 7）。通过静脉阻断体积描记法评估基础前臂血流量（FBF）、对动脉内乙酰胆碱（Ach）的内皮依赖性血管舒张以及对动脉内硝普钠的非内皮依赖性血管舒张。LCT和MCT输注均使基础FBF分别从1.58±0.35显著增加至2.60±0.76和2.28±0.56 mL/min 100 mL组织（均P < 0.05）。LCT加肝素时也观察到这种增加，但单独使用ASA后未观察到。与基线条件（436±44%）相比，LCT（最大Ach剂量时输注/对照臂比值的252±34%）和MCT（255±41%）期间Ach诱导的FBF增加百分比均降低（均P < 0.05）。LCT加ASA期间对Ach的反应也较低，而单独使用ASA时与基线相似。在各实验条件下对硝普钠的反应未观察到差异。总之，1）FFA对内皮依赖性血管舒张的影响与其链长无关；2）LCT和MCT均增加基础FBF，与环氧合酶抑制无关；3）急性给予ASA不影响内皮依赖性血管舒张。FFA对内皮对Ach反应的影响可能导致内皮功能改变，进而导致动脉粥样硬化性心血管疾病的发生和发展。
