Intravenous intralipid-induced blood pressure elevation and endothelial dysfunction in obese African-Americans with type 2 diabetes.
OBJECTIVE
Increased free fatty acids (FFAs) are leading candidates in the pathogenesis of insulin resistance and hypertension in obese subjects. We evaluated the effect of sustained elevations of FFA on blood pressure, endothelial function, insulin secretion, inflammatory markers, and renin-angiotensin system.


METHODS
Twenty-four obese, African-American, normotensive diabetic subjects received a sequential 48-h infusion of Intralipid (20%, 40 ml/h) plus heparin (250 units/h) or normal saline (40 ml/h) plus heparin (250 units/h).


RESULTS
Blood pressure was significantly increased within 4 h of lipid infusion and reached a peak increment of 13 mm Hg in systolic and 5 mm Hg in diastolic blood pressure at 24 h (P < 0.01). Compared to baseline, lipid infusion reduced flow-mediated dilatation by 11% at 24 h and 18% at 48 h (P < 0.001). FFA and triglyceride levels increased from a baseline of 0.5 +/- 0.2 mmol/liter and 135 +/- 76 mg/dl to 1.8 +/- 1.0 mmol/liter and 376 +/- 314 mg/dl at 48 h, respectively (P < 0.01). C-Reactive protein increased by 35% at 24 h and by 110% at 48 h of lipid infusion. There were no significant changes in plasma renin and aldosterone levels during lipid or saline infusions.


CONCLUSIONS
Increased FFA levels result in a rapid and sustained elevation in blood pressure, impaired endothelial function, and increased inflammatory markers in obese subjects with type 2 diabetes. The model of FFA-induced hypertension may be useful in examining disease mechanisms associated with the development of hypertension in obese subjects.
Umpierrez
Guillermo E
GE
Department of Medicine, General Clinical Research Center, Emory University School of Medicine, 49 Jesse Hill Jr. Drive, Atlanta, Georgia 30303, USA. geumpie@emory.edu
Smiley
Dawn
D
Robalino
Gonzalo
G
Peng
Limin
L
Kitabchi
Abbas E
AE
Khan
Bobby
B
Le
Ahn
A
Quyyumi
Arshed
A
Brown
Virgil
V
Phillips
Lawrence S
LS
D000328:Adult; D001741:Black or African American; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D012083:Renin / Q000097:blood; D014280:Triglycerides / Q000097:blood
D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D000450:Aldosterone; D002097:C-Reactive Protein; D012083:Renin