Heparin attenuates norepinephrine-induced venoconstriction

Abstract

Reversal by heparin of norepinephrine-induced constriction of normal hand veins was studied. Venous size was measured using a linear variable differential transformer (LVDT) during infusions of saline, norepinephrine, insulin and norepinephrine, and graded doses of heparin with norepinephrine. Heparin reduced the venoconstrictive effects of norepinephrine (p, 0.01), with the effects beginning at 18.5 nmol/min (0.05 U/min) and reaching a maximum between 185 nmol/min and 1.85 mmol/min (0.5 and 5 U/min). Maximal heparin-induced venorelaxation correlated with the maximal insulin effect within individuals (r = 0.8, p, 0.01) and was unchanged by the addition of insulin. Methylene blue, a non-specific inhibitor of the nitric oxide cGMP cascade, reduced heparin-induced venorelaxation. In conclusion, heparin in either physiologic or pharmacologic concentrations attenuated norepinephrine-induced venoconstriction. A common mechanism of venorelaxation by heparin and insulin is not excluded given the correlation and lack of additivity of maximum effects and their inhibition by methylene blue.