Intralipid Enhances α 1 -Adrenergic Receptor–Mediated Pressor Sensitivity

—The dyslipidemia in obese hypertensive persons may contribute to their increased vascular α-adrenergic receptor reactivity and tone. To further examine this notion, we conducted 2 studies of pressor sensitivity to phenylephrine, an α1 -adrenergic receptor agonist, in lean normotensive subjects. In the first study (n=6), pressor responses to phenylephrine were obtained before and during a saline and heparin infusion. On another day, pressor reactivity to phenylephrine was measured before and during infusion of 20% Intralipid at 0.5 mL · m−2 · min−1 with heparin at 1000 U/h to increase lipoprotein lipase activity and raise nonesterified fatty acids (NEFAs). In the second study (n=8), baseline reactivity to phenylephrine was obtained on 2 separate days 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 plasma NEFAs from baseline (516±90 versus 512±108 μmol/L, respectively;P =NS) or the dose of phenylephrine required to raise mean blood pressure by 20 mm Hg ([PD20PE ]; 1.00±0.14 versus 0.95±0.10 μg · kg−1 · min−1 , respectively,P =NS). Intralipid at 0.5 mL · m−2 · min−1 with heparin raised plasma NEFAs to 793±30 μmol/L per liter (P <0.05 versus baseline) and reduced PD20PE from 1.01±0.10 to 0.80±0.09 μg · kg−1 · min−1 (P <0.05). Compared with baseline, Intralipid alone increased plasma NEFAs to 946±80 μmol/L (P <0.05), and NEFAs increased further with the addition of heparin to 2990±254 μmol/L (P <0.01). Despite an apparently greater increase of plasma NEFAs with Intralipid and heparin, Intralipid alone and together with heparin similarly reduced PD20PE . Across all study conditions, changes in levels of triglycerides and NEFAs correlated with changes in mean arterial pressure responses to phenylephrine, especially at the 0.4-μg · kg−1 · min−1 infusion rate of phenylephrine (r =0.64,P <0.01 andr =0.54,P <0.01, respectively). These data suggest that raising levels of plasma NEFAs and/or triglycerides enhances α1 -adrenoceptor–mediated pressor sensitivity. The findings suggest that lipid abnormalities in obese hypertensives, which include elevated NEFAs and triglycerides, contribute to greater vascular α1 -adrenergic reactivity.