FATTY-ACIDS, NOT INSULIN, MODULATE ALPHA(1)-ADRENERGIC REACTIVITY IN DORSAL HAND VEINS

Resistance to the vasodilator action of insulin and its capacity to an tagonize vascular cu-adrenergic reactivity may contribute to the incre ased neurovascular tone and blood pressure in obese hypertensive subje cts. 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 alpha(1)-adrenoce ptor reactivity. Research by others suggests that insulin antagonizes alpha(1)-adrenoceptor tone in dorsal hand veins. Taken together with e vidence that NEFAs antagonize several of the metabolic actions of insu lin, these observations raise the possibility that NEFAs participate i n resistance to the vascular effects of insulin and suggest that dorsa l hand veins represent a good model for studying these interactions. T hus, we produced local hyperinsulinemia in the dorsal hand veins of si x lean normal volunteers and quantified changes of venous distensibili ty 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 ED50 (P<.01), but this alph a(1)-sensitizing action of NEFAs was not antagonized by insulin concen trations up to approximate to 1000 mu U/mL. Moreover, local hyperinsul inemia alone did not affect vascular alpha(1)-adrenergic sensitivity a s measured by the phenylephrine ED50. To address the possibility that the absence of an insulin effect reflected a lack of nitric oxide-medi ated, endothelium-dependent, dilation in hand veins, responses to acet ylcholine were obtained. Acetylcholine relaxed preconstricted hand vei ns by 60% to 80% (P<.01) in the presence and absence of indomethacin, which suggests substantial endothelium-dependent cyclooxygenase-indepe ndent vasodilation. The results confirm that raising NEFAs locally enh ances vascular alpha(1)-adrenoceptor sensitivity. Despite the presence of significant endothelium-dependent dilation in dorsal hand veins, i nsulin does not antagonize vascular alpha(1)-adrenoceptor sensitivity in the presence of either ambient or locally elevated fatty acids.