title: Effects of low-dose heparin infusion on arterial endothelin-1 release in humans.
abstract: BACKGROUND
  The aim of this study was to evaluate the effect of low-dose heparin infusion on arterialized endothelin-1 (ET-1) release in the presence of fasting or high insulin levels in healthy humans.
  
  
  RESULTS
  Eleven normal subjects underwent two tests in random order lasting 240 minutes. A primed (250 IU), continuous heparin (600 IU/h) infusion was performed in test 1; saline was infused in test 2 as control. At 120 minutes, a euglycemic hyperinsulinemic clamp (25 mU.kg-1.h-1) was started that lasted 2 hours in both tests. Two hours after heparin infusion (test 1), ET-1 levels decreased by 32% (3.52 +/- 0.60 to 3.02 +/- 0.73 pg/mL), while nitric oxide (NO) and forearm blood flow increased by 29% and 14%, respectively. During saline infusion, ET-1, nitric oxide, and forearm blood flow remained unchanged. There was a significant interaction between the effect of decreasing ET-1 levels and the heparin treatment (F, 4.06; df, 3.30; P < .01). The decrease in ET-1 levels was significantly correlated with the increase in forearm blood flow in test 1 (r = .74; P < .01) but not in test 2. During the heparin/insulin period, ET-1 increased by 25%, returning to fasting values; nitric oxide levels increased by 12%; and forearm blood flow remained unchanged.
  
  
  CONCLUSIONS
  The present study showed that it is possible to decrease ET-1 levels by use of low-dose heparin infusion in humans. This effect seems mediated by a simultaneous increase in nitric oxide levels and is completely reversed by a mild increase in insulin concentrations.
authors.affiliation: Istituto Scientifico H. San Raffaele, Cattedra di Clinica Medica, University of Milan, Italy.
authors.forename: P M
authors.initials: PM
authors.lastname: Piatti
authors.forename: L D
authors.initials: LD
authors.lastname: Monti
authors.forename: G
authors.initials: G
authors.lastname: Valsecchi
authors.forename: M
authors.initials: M
authors.lastname: Conti
authors.forename: R
authors.initials: R
authors.lastname: Nasser
authors.forename: B
authors.initials: B
authors.lastname: Guazzini
authors.forename: E
authors.initials: E
authors.lastname: Fochesato
authors.forename: C V
authors.initials: CV
authors.lastname: Phan
authors.forename: A E
authors.initials: AE
authors.lastname: Pontiroli
authors.forename: G
authors.initials: G
authors.lastname: Pozza
mesh_terms: D000328:Adult; D001158:Arteries / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D019332:Endothelin-1 / Q000378:metabolism*; D005215:Fasting; D005260:Female; D005542:Forearm / Q000098:blood supply; D006493:Heparin / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D019332:Endothelin-1; D007328:Insulin; D009569:Nitric Oxide; D006493:Heparin