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(Circulation. 1996;94:2703-2707.)
© 1996 American Heart Association, Inc.

Articles

Effects of Low-Dose Heparin Infusion on Arterial Endothelin-1 Release in Humans

P.M. Piatti, MD; L.D. Monti, MD; G. Valsecchi, MD; M. Conti, MD; R. Nasser, MD; B. Guazzini, MD; E. Fochesato, MD; C.V. Phan; A.E. Pontiroli, MD; G. Pozza, MD

the Istituto Scientifico H. San Raffaele, Cattedra di Clinica Medica, University of Milan, Italy.

Correspondence to PierMarco Piatti, MD, Istituto Scientifico H. San Raffaele, Via Olgettina 60, 20132 Milano, Italy.

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.

Methods and 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.

Key Words: heparin • insulin • endothelium-derived factors

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