Insulin modulation of an endothelial nitric oxide component present in the α2- and β-adrenergic responses in human forearm

Giuseppe Lembo, Guido Iaccarino, Carmine Vecchione, Emanuele Barbato, Raffaele Izzo, Dario Fontana, Bruno Trimarco

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We explored in 51 normal subjects, distributed in various series of experiments, whether endothelium nitric oxide may play a role in insulin modulation of α2- and β-adrenergic-evoked vascular responses. In particular, we examined the forearm blood flew response (FBF, ml·min- 1·dl-1) to intra-brachial infusion of BHT-933 (0.5, 1, and 2 μg·min- 1·dl-1) or isoproterenol (1, 3, and 6 ng·min-1·dl-1) in control conditions, during intrabrachial infusion of insulin alone (0.05 mU·kg- 1·min-1) and associated with L-N-monomethylarginine (L-NMMA) (0.05 μg·min-1·dl-1), a nitric oxide synthase inhibitor. In control conditions both BHT-933 and isoproterenol induced a dose-dependent vascular response. Local hyperinsulinemia (deep venous plasma insulin 68.5±4 μU/ml) did not change basal FBF whereas attenuated BHT-933 vasoconstriction and enhanced isoproterenol vasodilation. L-NMMA reduced basal FBF and abolished the insulin effect on BHT-933 and isoproterenol response. To clarify whether:a nitric oxide component is included in α2- and β-adrenergic response and may be responsible for insulin vascular effect, we further examined BHT-933 and isoproterenol responses during nitric oxide inhibition. Interestingly, L-NMMA potentiated the BHT-933 vasoconstriction and attenuated the isoproterenol vasodilation and, in these conditions, insulin was no more able to exhibit its vascular effects. Finally, to rule out the possibility that the conteracting effect of L-NMMA may not be specifically related to insulin action, dose-response curves to phenylephrine (0.5, 1, and 2 μg·min-1·dl-1) or sodium nitroprusside (1, 2, and 4 μg·min-1·dl- 1) were also performed. Both insulin and L-NMMA were unable to alter the phenylephrine-induced vasoconstriction and the sodium nitroprusside vasodilation. In conclusion, our data demonstrate an endothelial nitric oxide component in the α2- and β-adrenergic vascular responses which is the target of the insulin vascular action.

Original languageEnglish
Pages (from-to)2007-2014
Number of pages8
JournalJournal of Clinical Investigation
Issue number8
Publication statusPublished - Oct 15 1997


  • Adrenergic receptors
  • Endothelium
  • Forearm blood flow
  • Insulin
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Medicine(all)


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