Fatty acids enhance neurovascular reflex responses by effects on alpha 1-adrenoceptors

Abnormalities in plasma nonesterified fatty acids (NEFAs) may contribute to increased vascular alpha-adrenergic tone in obese hypertensive patients, because raising NEFAs locally enhances vascular reactivity to exogenously infused phenylephrine. However, responses to exogenous phenylephrine, a relatively selective alpha 1-adrenoceptor agonist, may not reflect the physiologically more important response to endogenous norepinephrine, a nonselective alpha-adrenoceptor agonist. To study the effects of NEFAs on vascular responses to endogenously released norepinephrine, dorsal hand venoconstrictor responses to thigh cuff inflation were quantified in nine healthy volunteers during coinfusion of Intralipid with heparin to raise fatty acids locally. Intralipid-heparin, which approximately doubled local linoleic and oleic acid concentrations (P < 0.05), increased the magnitude and duration of the venoconstrictor response to thigh cuff inflation (P < 0.005) and also enhanced venoconstrictor responses to locally infused phenylephrine but not clonidine, a relatively selective partial alpha 2-adrenoceptor agonist. The results of this study indicate that NEFAs enhance reflex vasoconstrictor responses largely through local effects on the vascular alpha 1-adrenoceptor and raise the possibility that fatty acids contribute to increased neurovascular tone in obese hypertensive patients.