Fatty Acids, Not Insulin, Modulate α 1 -Adrenergic Reactivity in Dorsal Hand Veins

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Abstract
Resistance to the vasodilator action of insulin and its capacity to antagonize vascular α-adrenergic reactivity may contribute to the increased neurovascular tone and blood pressure in obese hypertensive subjects. We showed that nonesterified fatty acids (NEFAs) were elevated in obese hypertensive subjects and that raising NEFAs locally in dorsal hand veins of healthy normotensive subjects enhances α 1 -adrenoceptor reactivity. Research by others suggests that insulin antagonizes α 1 -adrenoceptor tone in dorsal hand veins. Taken together with evidence that NEFAs antagonize several of the metabolic actions of insulin, these observations raise the possibility that NEFAs participate in resistance to the vascular effects of insulin and suggest that dorsal hand veins represent a good model for studying these interactions. Thus, we produced local hyperinsulinemia in the dorsal hand veins of six lean normal volunteers and quantified changes of venous distensibility in response to phenylephrine in the presence and absence of a local elevation of NEFAs. We confirmed that raising NEFAs locally decreased by twofold to threefold the phenylephrine ED 50 ( P <.01), but this α 1 -sensitizing action of NEFAs was not antagonized by insulin concentrations up to ≈1000 μU/mL. Moreover, local hyperinsulinemia alone did not affect vascular α 1 -adrenergic sensitivity as measured by the phenylephrine ED 50 . To address the possibility that the absence of an insulin effect reflected a lack of nitric oxide–mediated, endothelium-dependent dilation in hand veins, responses to acetylcholine were obtained. Acetylcholine relaxed preconstricted hand veins by 60% to 80% ( P <.01) in the presence and absence of indomethacin, which suggests substantial endothelium-dependent, cyclooxygenase-independent vasodilation. The results confirm that raising NEFAs locally enhances vascular α 1 -adrenoceptor sensitivity. Despite the presence of significant endothelium-dependent dilation in dorsal hand veins, insulin does not antagonize vascular α 1 -adrenoceptor sensitivity in the presence of either ambient or locally elevated fatty acids.