INTRALIPID ENHANCES ALPHA(1)-ADRENERGIC RECEPTOR-MEDIATED PRESSOR SENSITIVITY

The dyslipidemia in obese hypertensive persons may contribute to their increased vascular alpha-adrenergic receptor reactivity and tone. To further examine this notion, we conducted 2 studies of presser sensiti vity to phenylephrine, an alpha(1)-adrenergic receptor agonist, in lea n normotensive subjects. In the first study (n=6), presser responses t o phenylephrine were obtained before and during a saline and heparin i nfusion. On another day, presser reactivity to phenylephrine was measu red before and during infusion of 20% Intralipid at 0.5 mL . m(-2) . m in(-1) with heparin at 1000 U/h to increase lipoprotein lipase activit y and raise nonesterified fatty acids (NEFAs). In the second study (n= 8), baseline reactivity to phenylephrine was obtained on 2 separate da ys and repeated after raising NEFAs and triglycerides either with 0.8 mL . m(-2) . min(-1) of 20% Intralipid alone or together with heparin. The infusion of saline and heparin did not significantly change plasm a NEFAs from baseline (516+/-90 versus 512+/-108 mu mol/L, respectivel y; P=NS) or the dose of phenylephrine required to raise mean blood pre ssure by 20 mm Hg ([PD20PE]; 1.00+/-0.14 versus 0.95+/0.10 mu g . kg(- 1) . min(-1), respectively, P=NS). Intralipid at 0.5 mL . m(-2) . min( -1) with heparin raised plasma NEFAs to 793+/-30 mu mol/L per liter (P <0.05 versus baseline) and reduced PD20PE from 1.01+/-0.10 to 0.80+/-0 .09 mu g . kg(-1) . min(-1) (P<0.05). Compared with baseline, Intralip id alone increased plasma NEFAs to 946+/-80 mu mol/L (P<0.05), and NEF As increased further with the addition of heparin to 2990+/-254 mu mol /L (P<0.01). Despite an apparently greater increase of plasma NEFAs wi th Intralipid and heparin, Intralipid alone and together with heparin similarly reduced PD20PE. Across all study conditions, changes in leve ls of triglycerides and NEFAs correlated with changes in mean arterial pressure responses to phenylephrine, especially at the 0.4-mu g . kg( -1) . min(-1) infusion rate of phenylephrine (r=0.64, P<0.01 and r=0.5 4, P<0.01, respectively). These data suggest that raising levels of pl asma NEFAs and/or triglycerides enhances alpha(1)-adrenoceptor-mediate d presser sensitivity. The findings suggest that lipid abnormalities i n obese hypertensives, which include elevated NEFAs and triglycerides, contribute to greater vascular alpha(1)-adrenergic reactivity.