Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation
Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation
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DOI：
10.1172/jci119636
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发表时间：
1997-09-01
影响因子：
15.9
通讯作者：
Baron, AD
中科院分区：
文献类型：
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作者：
Steinberg, HO;Tarshoby, M;Baron, AD
我们最近发现胰岛素抵抗性肥胖患者内皮功能受损。在这里，我们检验了这样一个假设，即循环FFA升高到胰岛素抵抗受试者的水平会损害内皮功能，我们研究了在输注生理盐水期间和通过低或高浓度内分泌提高全身循环FFA水平后，股动脉内输注内皮依赖性血管扩张剂氯化乙酰甲胆碱（Mch）或内皮非依赖性血管扩张剂硝普钠时腿部血流反应。在瘦的健康人群中，通过输注生长抑素（SRIF）或内源性输注Intraperoid加肝素的剂量输注来产生胰岛素减少症，在输注Intraperoid加肝素2小时后，FFA水平从562+/-95 μ mol增加到1，303 +/-188 μ mol，从350+/-35 μ mol增加到3，850+/-371 μ mol（P < 0.001）与生理盐水相比，两组中，随着FFA水平的升高，MCH诱导的血管舒张相对于基线降低了约20%（P < 0.05，生理盐水与FFA，ANOVA）。相反，相似的FFA升高并没有改变腿部对硝普钠的血流反应。在2小时SRIF输注期间，胰岛素水平下降，FFA水平从474+/-22上升到1,042+/-116 μ mol（P < 0.01）; MCH诱导的血管舒张减少了20%（P < 0.02，生理盐水vs，SRIF，ANOVA）。在SRIF期间更换基础胰岛素水平导致FFA水平从545+/-47降至228+/-61 μ mol，并防止单独使用SRIF时观察到的Mch诱导的血管舒张受损。总之，（a）循环FFA水平升高导致内皮功能障碍，和（B）胰岛素抗性人中受损的内皮功能可能继发于在这些患者中观察到的升高的FFA浓度。
We have recently shown that insulin-resistant obese subjects exhibit impaired endothelial function. Here, we test the hypothesis that elevation of circulating FFA to levels seen in insulin-resistant subjects can impair endothelial function, We studied leg blood flow responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) or the endothelium-independent vasodilator sodium nitroprusside during the infusion of saline and after raising systemic circulating FFA levels esogenously via a low-or high-dose infusion of Intralipid plus heparin or endogenously by an infusion of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy humans, After 2 h of infusion of Intralipid plus heparin, FFA levels increased from 562+/-95 to 1,303+/-188 mu mol, and from 350+/-35 to 3,850+/-371 mu mol (P < 0.001) vs. saline for both low-and high-dose groups, respectively, Mch-induced vasodilation relative to baseline was reduced by similar to 20% in response to the raised FFA levels in both groups (P < 0.05, saline vs, FFA, ANOVA). In contrast, similar FFA elevation did not change leg blood flow responses to sodium nitroprusside, During the 2-h SRIF infusion, insulin levels fell, and FFA levels rose from 474+/-22 to 1,042+/-116 mu mol (P < 0.01); Mch-induced vasodilation was reduced by similar to 20% (P < 0.02, saline vs, SRIF, ANOVA). Replacement of basal insulin levels during SRIF resulted in a fall of FFA levels from 545+/-47 to 228+/-61 mu mol, and prevented the impairment of Mch-induced vasodilation seen with SRIF alone, In conclusion, (a) elevated circulating FFA levels cause endothelial dysfunction, and (b) impaired endothelial function in insulin-resistant humans may be secondary to the elevated FFA concentrations observed in these patients.