Fatty acids enhance vascular alpha-adrenergic sensitivity.
Hypertensive patients are heavier and have a more centralized body fat distribution, which is associated with risk factor clustering and resistance to insulin's actions, including suppression of plasma nonesterified fatty acids. We postulated that abnormalities of nonesterified fatty acids contribute to the increased vascular alpha-adrenergic reactivity and tone observed in our previous studies of obese hypertensive subjects. To test this hypothesis, in two separate protocols 10% Intralipid was infused into a dorsal hand vein with heparin to activate lipoprotein lipase and raise fatty acid levels locally. In protocol 1, the effects of Intralipid/heparin compared with those of 5% dextrose/heparin on dorsal hand vein sensitivity to phenylephrine were assessed by use of the linear variable differential transformer technique in 8 normotensive subjects. In protocol 2, the effects of Intralipid/heparin were compared with those of saline/heparin on hand vein responses to both phenylephrine and angiotensin II in 11 normotensive African American women. Intralipid/heparin reduced the dose of phenylephrine required to produce 50% of the maximal venoconstrictor response from 582 to 137 ng/min (compared with dextrose/heparin, P < .01) in protocol 1 and from 293 to 137 ng/min (compared with saline/heparin, P < .01) in protocol 2. Intralipid/heparin did not significantly alter hand vein responses to angiotensin compared with saline/heparin. These data suggest that abnormalities of nonesterified fatty acids in obese hypertensive patients with risk factor clustering may contribute to their increased neurovascular tone.
Stepniakowski
K T
KT
Department of Pharmacology, Medical University of South Carolina, Charleston 29425, USA.
Goodfriend
T L
TL
Egan
B M
BM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D044383:Black People; D001808:Blood Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D014661:Vasoconstriction; D001741:Black or African American
D000316:Adrenergic alpha-Agonists; D004338:Drug Combinations; D005217:Fat Emulsions, Intravenous; D005227:Fatty Acids; D000804:Angiotensin II; D010656:Phenylephrine; D006493:Heparin