title: Modulation of vasoconstriction by insulin.
abstract: OBJECTIVE
  To test the hypothesis that insulin differently modifies vasoconstriction and recovery from vasoconstriction induced by endogenously released versus circulating norepinephrine, and to investigate the time-dependency of its effect
  
  
  METHODS
  Healthy male subjects were studied. Norepinephrine was infused for 10 min into the brachial artery with 40 min pauses in between, three times with vehicle and three times during concurrent intra-arterial infusion of 0.1 mU/kg per min insulin, inducing locally high, above physiologic, concentrations of insulin. We infused tyramine, to release endogenous norepinephrine from sympathetic nerve endings, similarly into six other subjects. Ratios of infused: control arm forearm blood flow (FBFi: FBFc) were determined during the infusions of agonists and for 10 min after their cessation. Because of insulin's vasodilator effect, responses to norepinephrine after vasodilatation by isoproterenol or sodium nitroprusside were also determined for six other subjects.
  
  
  RESULTS
  Exogenous norepinephrine induced a transient peak vasoconstriction and then a partial recovery from vasoconstriction that remained stable throughout the infusion. Administration of norepinephrine decreased the FBFi: FBFc ratio by 29+/-7% (mean +/- SEM) before and 45+/-4% during infusion of insulin (P < 0.01). After cessation of the norepinephrine infusions blood flow rapidly recovered, which even resulted in an overshoot vasodilatation during infusion of insulin. Administration of tyramine induced only a plateau vasoconstrictor phase; the FBFi: FBFc ratio decreased by 49+/-6% before and 63+/-5% during infusion of insulin (P < 0.01). After cessation of the tyramine infusions, vasoconstriction slowly and only partially recovered, which was not affected by infusion of insulin. No time-dependency was observed for the repeated infusions of agonist. Infusion of insulin significantly reduced the apparent concentrations of norepinephrine and tyramine at which half maximal effect occurs (EC50). Dilatation with isoproterenol or sodium nitroprusside beforehand dose-dependently also reduced the EC50 of norepinephrine, with a correlation coefficient of 0.613 (P < 0.001) for relationship between individual EC50 values and baseline flows.
  
  
  CONCLUSIONS
  Vasoconstriction induced by exogenous or endogenous norepinephrine is augmented by a high concentration of insulin. This augmentation is not time-dependent This augmentation is, however, an unspecific effect insofar as other vasodilators also enhance norepinephrine-induced vasoconstriction. The finding that hyperinsulinemia stimulates norepinephrine's vasoconstrictor effect implies that these two growth-stimulating and vascular hypertrophy-stimulating factors may act synergistically on vascular remodeling in patients with hypertension and hyperinsulinemia.
authors.affiliation: Department of Nephrology, University Hospital, Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van Veen
authors.forename: P C
authors.initials: PC
authors.lastname: Chang
mesh_terms: D000328:Adult; D006801:Humans; D007261:Infusions, Intra-Arterial; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008955:Models, Cardiovascular; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000502:physiology; D013997:Time Factors; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D007328:Insulin; D009599:Nitroprusside; D007545:Isoproterenol; D009638:Norepinephrine; D014439:Tyramine