Horm Metab Res 2018; 50(06): 478-484
DOI: 10.1055/a-0620-8438
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Cardiovascular Effects of Stress During Acutely Increased Free Fatty Acids in a Randomized, Double-Blind, Cross-Over Study in Humans

Safoura Sheikh Rezaei
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Brigitte Litschauer
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Gazaleh Gouya
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Sabina Baumgartner-Parzer
2   Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria
,
Thomas Stulnig
2   Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria
,
Michael Wolzt
1   Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

received 05 May 2017

accepted 10 April 2018

Publication Date:
08 June 2018 (online)

Abstract

Increased free fatty acids stimulate sympathetic nervous system activity, impair endothelium-dependent vasodilation, and increase regional blood flow. The aim of this study was to assess if fatty acids acutely elevated by infusion of intralipid/heparin affect cardiovascular reactivity employing two stressors eliciting either a cardiac (Stroop test) or vascular (Cold Face test) dominated pressor response. Two stress tasks were performed in 20 healthy subjects (10 women, 10 men) before and during a 180-min intralipid/heparin or saline infusion as placebo on alternate trial days in a randomized crossover study design. Blood pressure, heart rate, cardiac index, and total peripheral resistance index were measured. At baseline, the Stroop test did not affect hemodynamic parameters, and the Cold Face test had an impact on hemodynamic parameters except for heart rate. Plasma fatty acids concentrations increased to 810% (t=11.0, p<0.001) of baseline and C-peptide increased by 17% (t=4.66, p<0.001) during intralipid/heparin infusion. This was paralleled by increased cardiac index (F=9.98; p<0.005 vs. saline) and reduced total peripheral resistance index (F=4.46; p<0.05 vs saline). There was no effect of intralipid/heparin or saline infusion on Stroop test or Cold Face test reactivity of hemodynamic parameters. An acute increase in free fatty acids does not affect the magnitude or pattern of stress response in healthy volunteers, but primarily alter the underlying cardiovascular tone by decreasing total peripheral resistance index and increasing cardiac index to maintain a constant blood pressure.

 
  • References

  • 1 Beegom R, Singh RB. Association of higher saturated fat intake with higher risk of hypertension in an urban population of Trivandrum in south India. Int J Cardiol 1997; 58: 63-70
  • 2 Damjanovic M, Barton M. Fat intake and cardiovascular response. Curr Hypertens Rep 2008; 10: 25-31
  • 3 Ishibashi Y, Matsui T, Yamagishi S. Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation. Horm Metab Res 2016; 48: 191-195
  • 4 Belviranli M, Okudan N, Celik F. Association of Circulating Irisin with Insulin Resistance and Oxidative Stress in Obese Women. Horm Metab Res 2016; 48: 653-657
  • 5 Bayerle-Eder M, Polska E, Kopf A, Roden M, Waldhausl W, Pleiner H, Wipler B, Wolzt M, Schmetterer L. Free fatty acids exert a greater effect on ocular and skin blood flow than triglycerides in healthy subjects. Eur J Clin Invest 2004; 34: 519-526
  • 6 Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, Bayazeed B, Baron AD. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest 1997; 100: 1230-1239
  • 7 Langenberger H, Schaller G, Pleiner J, Mittermayer F, Bayerle-Eder M, Wolzt M. C- eptide has no effect on forearm blood flow during local hyperinsulinaemia in healthy humans. Br J Clin Pharmacol 2003; 55: 526-530
  • 8 Gosmanov AR, Smiley DD, Robalino G, Siquiera J, Khan B, Le NA, Patel RS, Quyyumi AA, Peng L, Kitabchi AE, Umpierrez GE. Effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects. Am J Physiol Endocrinol Metab 2010; 299: E953-E958
  • 9 Stojiljkovic MP, Zhang D, Lopes HF, Lee CG, Goodfriend TL, Egan BM. Hemodynamic effects of lipids in humans. Am J Physiol Regul Integr Comp Physiol 2001; 280: R1674-R1679
  • 10 Paolisso G, Manzella D, Rizzo MR, Ragno E, Barbieri M, Varricchio G, Varricchio M. Elevated plasma fatty acid concentrations stimulate the cardiac autonomic nervous system in healthy subjects. Am J Clin Nutr 2000; 72: 723-730
  • 11 Polak K, Schmetterer L, Luksch A, Gruber S, Polska E, Peternell V, Bayerle-Eder M, Wolzt M, Krebs M, Roden M. Free fatty acids/triglycerides increase ocular and subcutaneous blood flow. Am J Physiol Regul Integr Comp Physiol 2001; 280: R56-R61
  • 12 Gadegbeku CA, Shrayyef MZ, Taylor TP, Egan BM. Mechanism of lipid enhancement of alpha1-adrenoceptor pressor sensitivity in hypertension. J Hypertens 2006; 24: 1383-1389
  • 13 Gadegbeku CA, Dhandayuthapani A, Sadler ZE, Egan BM. Raising lipids acutely reduces baroreflex sensitivity. Am J Hypertens 2002; 15: 479-485
  • 14 Florian JP, Pawelczyk JA. Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans. Clin Sci (London, England: 1979) 2010; 118: 61-69
  • 15 La Marca R, Waldvogel P, Thorn H, Tripod M, Wirtz PH, Pruessner JC, Ehlert U. Association between Cold Face Test-induced vagal inhibition and cortisol response to acute stress. Psychophysiology 2011; 48: 420-429
  • 16 Stemper B, Hilz MJ, Rauhut U, Neundorfer B. Evaluation of cold face test bradycardia by means of spectral analysis. Clin Auton Res 2002; 12: 78-83
  • 17 Khurana RK, Watabiki S, Hebel JR, Toro R, Nelson E. Cold face test in the assessment of trigeminal-brainstem-vagal function in humans. Ann Neurol 1980; 7: 144-149
  • 18 Willemsen GH, DeGeus EJ, Klaver CH, VanDoornen LJ, Carrofl D. Ambulatory monitoring of the impedance cardiogram. Psychophysiology 1996; 33: 184-193
  • 19 Krebs M, Stingl H, Nowotny P, Weghuber D, Bischof M, Waldhausl W, Roden M. Prevention of in vitro lipolysis by tetrahydrolipstatin. Clin Chem 2000; 46: 950-954
  • 20 Pleiner J, Schaller G, Mittermayer F, Bayerle-Eder M, Roden M, Wolzt M. FFA-induced endothelial dysfunction can be corrected by vitamin C. J Clin Endocrinol Metab 2002; 87: 2913-2917
  • 21 Nolan CJ, Madiraju MS, Delghingaro-Augusto V, Peyot ML, Prentki M. Fatty acid signaling in the beta-cell and insulin secretion. Diabetes 2006; 55 (Suppl. 02) S16-S23
  • 22 Morgan NG, Dhayal S. G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell. Biochem Pharmacol 2009; 78: 1419-1427
  • 23 Ahren B. Autonomic regulation of islet hormone secretion--implications for health and disease. Diabetologia 2000; 43: 393-410
  • 24 Burns SF, Kelsey SF, Arslanian SA. Effects of an intravenous lipid challenge and free fatty acid elevation on in vivo insulin sensitivity in African American versus Caucasian adolescents. Diabetes Care 2009; 32: 355-360
  • 25 Lindgren O, Carr RD, Deacon CF, Holst JJ, Pacini G, Mari A, Ahren B. Incretin hormone and insulin responses to oral versus intravenous lipid administration in humans. J Clin Endocrinol Metab 2011; 96: 2519-2524
  • 26 de Kreutzenberg SV, Crepaldi C, Marchetto S, Calo L, Tiengo A, Del Prato S, Avogaro A. Plasma free fatty acids and endothelium-dependent vasodilation: effect of chain-length and cyclooxygenase inhibition. J Clin Endocrinol Metab 2000; 85: 793-798
  • 27 Kearney MT, Chowienczyk PJ, Brett SE, Sutcliffe A, Ritter JM, Shah AM. Acute haemodynamic effects of lipolysis-induced increase of free fatty acids in healthy men. Clin Sci (London, England: 1979) 2002; 102: 495-500
  • 28 Fugmann A, Millgard J, Sarabi M, Berne C, Lind L. Central and peripheral haemodynamic effects of hyperglycaemia, hyperinsulinaemia, hyperlipidaemia or a mixed meal. Clin Sci (London, England: 1979) 2003; 105: 715-721
  • 29 Monahan KD, Dyckman DJ, Ray CA. Effect of acute hyperlipidemia on autonomic and cardiovascular control in humans. Journal of Applied Physiology (Bethesda, Md: 1985) 2007; 103: 162-169
  • 30 Holland DJ, Erne D, Kostner K, Leano R, Haluska BA, Marwick TH, Sharman JE. Acute elevation of triglycerides increases left ventricular contractility and alters ventricular-vascular interaction. Am J Physiol Heart Circulat Physiol 2011; 301: H123-H128
  • 31 Bulow J, Madsen J, Hojgaard L. Reversibility of the effects on local circulation of high lipid concentrations in blood. Scand J Clin Lab Invest 1990; 50: 291-296
  • 32 Bulow J, Madsen J, Astrup A, Christensen NJ. Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo. Acta Physiol Scand 1985; 125: 661-667
  • 33 Manzella D, Barbieri M, Rizzo MR, Ragno E, Passariello N, Gambardella A, Marfella R, Giugliano D, Paolisso G. Role of free fatty acids on cardiac autonomic nervous system in noninsulin-dependent diabetic patients: Effects of metabolic control. J Clin Endocrinol Metab 2001; 86: 2769-2774
  • 34 Gosmanov AR, Smiley DD, Robalino G, Siquiera J, Khan B, Le N-A, Patel RS, Quyyumi AA, Peng L, Kitabchi AE, Umpierrez GE. Effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects. Am J Physiol Endocrinol Metab 2010; 299: E953-E958
  • 35 Garafova A, Penesova A, Cizmarova E, Marko A, Vlcek M, Jezova D. Cardiovascular and sympathetic responses to a mental stress task in young patients with hypertension and/or obesity. Physiol Res/Academia Scientiarum Bohemoslovaca 2014; (Suppl. 04) S459-S467
  • 36 Barbosa DF, Prada FJ, Glanner MF, Nobrega Ode T, Cordova CO. Cardiovascular response to Stroop test: Comparison between the computerized and verbal tests. Arquiv Brasil Cardiol 2010; 94: 507-511
  • 37 Saab PG, Llabre MM, Hurwitz BE, Schneiderman N, Wohlgemuth W, Durel LA, Massie C, Nagel J. The cold pressor test: Vascular and myocardial response patterns and their stability. Psychophysiology 1993; 30: 366-373
  • 38 Grekin RJ, Vollmer AP, Sider RS. Pressor effects of portal venous oleate infusion. A proposed mechanism for obesity hypertension. Hypertension 1995; 26: 193-198
  • 39 Storlien LH, Hulbert AJ, Else PL. Polyunsaturated fatty acids, membrane function and metabolic diseases such as diabetes and obesity. Curr Opin Clin Nutr Metab Care 1998; 1: 559-563
  • 40 Storlien LH, Baur LA, Kriketos AD, Pan DA, Cooney GJ, Jenkins AB, Calvert GD, Campbell LV. Dietary fats and insulin action. Diabetologia 1996; 39: 621-631