Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. Export

@article{citeulike:254141, 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.}, address = {Department of Medicine, Indiana University Medical Center, Indianapolis, Indiana 46202, USA.}, author = {Steinberg, H. O. and Tarshoby, M. and Monestel, R. and Hook, G. and Cronin, J. and Johnson, A. and Bayazeed, B. and Baron, A. D.}, citeulike-article-id = {254141}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/9276741}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=9276741}, day = {1}, issn = {0021-9738}, journal = {J Clin Invest}, keywords = {endothelialfunction, endothelium, fattyacids, ffa, human, invivo}, month = {September}, number = {5}, pages = {1230--1239}, posted-at = {2005-07-13 12:03:15}, priority = {2}, title = {Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/9276741}, volume = {100}, year = {1997} }

TY - JOUR ID - citeulike:254141 L3 - citeulike-article-id:254141 N2 - 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. IS - 5 JF - J Clin Invest SN - 0021-9738 AD - Department of Medicine, Indiana University Medical Center, Indianapolis, Indiana 46202, USA. EP - 1239 TI - Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. VL - 100 SP - 1230 KW - endothelialfunction KW - endothelium KW - fattyacids KW - ffa KW - human KW - invivo AU - Steinberg, HO AU - Tarshoby, M AU - Monestel, R AU - Hook, G AU - Cronin, J AU - Johnson, A AU - Bayazeed, B AU - Baron, AD PY - 1997/09/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/9276741 ER -