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Cited by 761Nitric Oxide and Endothelin EffectsDiabetes, Cardiovascular Risks, and LipoproteinsCardiovascular Function and Risk Factors

The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation

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Steinberg, H O, Tarshoby, M, Monestel, R, Hook, G, Cronin, J, Johnson, A, Bayazeed, B, Baron, A D·1997·Journal of Clinical Investigation
DOI 10.1172/jci119636PMC PMC508300
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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 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 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 micromol, and from 350+/-35 to 3,850+/-371 micromol (P < 0.001) vs. saline for both low- and high-dose groups, respectively. Mch-induced vasodilation relative to baseline was reduced by approximately 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 micromol (P < 0.01); Mch-induced vasodilation was reduced by approximately 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 micromol, 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.

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Metadata

Authors
Steinberg, H. O., Tarshoby, M., Monestel, R., Hook, G., Cronin, J., Johnson, A., Bayazeed, B., & Baron, A. D.
Affiliations
  • Indiana University (US)
  • Indiana University – Purdue University Indianapolis (US)
ORCID
Tarshoby, M
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1997-09-01
Volume
100
Issue
5
Pages
1230-1239
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci119636
PMC
PMC508300
OpenAlex
W2086785365
Cited by
761
References
16
Citations by year
2026: 6 · 2025: 12 · 2024: 17 · 2023: 20 · 2022: 9 · 2021: 19 · 2020: 29 · 2019: 11 · 2018: 19 · 2017: 20 · 2016: 12 · 2015: 22 · 2014: 17 · 2013: 28 · 2012: 33
FWCI
10.61
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • American Heart Association
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 20452, DK42469)
  • National Center for Research Resources (MO1-RR75019)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
free fatty acids, endothelial dysfunction, endothelium-dependent vasodilation, insulin resistance, methacholine, sodium nitroprusside, leg blood flow, somatostatin, insulin deficiency, Intralipid, obesity, insulin replacement therapy
MeSH terms
Adult, Blood Pressure, Endothelium, Vascular, Fat Emulsions, Intravenous, Fatty Acids, Nonesterified, Female, Humans, Insulin, Leg, Male, Nitroprusside, Somatostatin, Vasodilation, Methacholine Chloride

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