Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation

Helmut Steinberg, Manal Tarshoby, Robert Monestel, Ginger Hook, Jessica Cronin, Ann Johnson, Basel Bayazeed, Alain D. Baron

Research output: Contribution to journalArticle

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Abstract

We have recently shown that insulin-resistant obese subjects exhibit impaired endothelial function. Here, we test the hypothesis that elevation of circulating NFA 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 exogenously 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 μmol, and from 350 ± 35 to 3,850 ± 371 μmol (P < 0.001) vs. saline for both low- and high-dose groups, respectively. Mch-induced vasodilation relative to baseline was reduced by ~ 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 μmol (P < 0.01); Mch-induced vasodilation was reduced by ~ 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 μmol, 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.

Original languageEnglish (US)
Pages (from-to)1230-1239
Number of pages10
JournalJournal of Clinical Investigation
Volume100
Issue number5
DOIs
StatePublished - Sep 1 1997

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Nonesterified Fatty Acids
Vasodilation
Methacholine Chloride
Endothelium
Insulin
Nitroprusside
Heparin
Leg
Analysis of Variance
Endothelium-Dependent Relaxing Factors
Somatostatin
Vasodilator Agents
Arteries
phospholipid emulsion soybean oil

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Steinberg, H., Tarshoby, M., Monestel, R., Hook, G., Cronin, J., Johnson, A., ... Baron, A. D. (1997). Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. Journal of Clinical Investigation, 100(5), 1230-1239. https://doi.org/10.1172/JCI119636

Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. / Steinberg, Helmut; Tarshoby, Manal; Monestel, Robert; Hook, Ginger; Cronin, Jessica; Johnson, Ann; Bayazeed, Basel; Baron, Alain D.

In: Journal of Clinical Investigation, Vol. 100, No. 5, 01.09.1997, p. 1230-1239.

Research output: Contribution to journalArticle

Steinberg, H, Tarshoby, M, Monestel, R, Hook, G, Cronin, J, Johnson, A, Bayazeed, B & Baron, AD 1997, 'Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation', Journal of Clinical Investigation, vol. 100, no. 5, pp. 1230-1239. https://doi.org/10.1172/JCI119636
Steinberg, Helmut ; Tarshoby, Manal ; Monestel, Robert ; Hook, Ginger ; Cronin, Jessica ; Johnson, Ann ; Bayazeed, Basel ; Baron, Alain D. / Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 5. pp. 1230-1239.
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