INSULIN MODULATION OF AN ENDOTHELIAL NITRIC-OXIDE COMPONENT PRESENT IN THE ALPHA(2)-ADRENERGIC AND BETA-ADRENERGIC RESPONSES IN HUMAN FOREARM

We explored in 51 normal subjects, distributed in various series of ex periments, whether endothelium nitric oxide may play a role in insulin modulation of alpha(2)- beta-adrenergic-evoked vascular responses. In particular, we examined the forearm blood flow response (FBF, ml.min( -1).dl(-1)) to intrabrachial infusion of BHT-933 (0.5, 1, and 2 mu g.m in(-1).dl(-1)) or isoproterenol (1, 3, and 6 ng.min(-1).dl(-1)) in con trol conditions, during intrabrachial infusion of insulin alone (0.05 mU.kg(-1).min(-1)) and associated with L-N-monomethylarginine (L-NMMA) (0.05 mu g.min(-1).dl(-1)), a nitric oxide synthase inhibitor. In con trol conditions both BHT-933 and isoproterenol induced a dose-dependen t vascular response. Local hyperinsulinemia (deep venous plasma insuli n 68.5+/-4 mu U/ml) did not change basal FBF whereas attenuated BHT-93 3 vasoconstriction and enhanced isoproterenol vasodilation. L-NMMA red uced basal FBF and abolished the insulin effect on BHT-933 and isoprot erenol response, To clarify whether a nitric oxide component is includ ed in alpha(2)- and beta-adrenergic response and may be responsible fo r insulin vascular effect, we further examined BHT-933 and isoproteren ol responses during nitric oxide inhibition. Interestingly, L-NMMA pot entiated the BHT-933 vasoconstriction and attenuated the isoproterenol vasodilation and, in these conditions, insulin was no more able to ex hibit its vascular effects. Finally, to rule out the possibility that the conteracting effect of L-NMMA may not be specifically related to i nsulin action, dose-response curves to phenylephrine (0.5, 1, and 2 mu g.min(-1).dl(-1)) or sodium nitroprusside (1, 2, and 4 mu g.min(-1).d l(-1)) were also performed. Both insulin and L-NMMA were unable to alt er the phenylephrine-induced vasoconstriction and the sodium nitroprus side vasodilation. In conclusion, our data demonstrate an endothelial nitric oxide component in the alpha(2)- and beta-adrenergic vascular r esponses which is the target of the insulin vascular action.