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 res istance to insulin's actions, including suppression of plasma nonester ified fatty acids. We postulated that abnormalities of nonesterified f atty acids contribute to the increased vascular alpha-adrenergic react ivity and tone observed in our previous studies of obese hypertensive subjects. To test this hypothesis, in two separate protocols 10% Intra lipid was infused into a dorsal hand vein with heparin to activate lip oprotein lipase and raise fatty acid levels locally. In protocol 1, th e effects of Intralipid/heparin compared with those of 5% dextrose/hep arin on dorsal hand vein sensitivity to phenylephrine were assessed by use of the linear variable differential transformer technique in 8 no rmotensive subjects. In protocol 2, the effects of Intralipid/heparin were compared with those of saline/heparin on hand vein responses to b oth phenylephrine and angiotensin II in 11 normotensive African Americ an women. Intralipid/heparin reduced the dose of phenylephrine require d to produce 50% of the maximal venoconstrictor response from 582 to 1 37 ng/min (compared with dextrose/heparin, P<.01) in protocol 1 and fr om 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 patie nts with risk factor clustering may contribute to their increased neur ovascular tone.