Hydroxyethyl Starch Inhibits Endothelium-Derived Relaxation in Porcine Coronary Arteries

Abstract

Objective: Hydroxyethyl starch (HES) solutions are widely used for fluid resuscitation. We studied the effects of HES on endothelium-dependent relaxation (EDR), especially on the endothelium-derived hyperpolarizing factor (EDHF). Methods: Four-millimeter-long rings of fresh porcine coronary arteries from the local slaughterhouse were consecutively tested with or without HES (6 mg/ml). Indomethacin (10 µmol/l) was added in all measurements to eliminate prostacyclin effects. Prostaglandin F2α (10 µmol/l) was used for contraction and bradykinin (10^–10 to 10^–5 mol/l) for inducing EDR, which was calculated in percentage of the precontraction. After blocking all nitric oxide formation by N-nitro-L-arginine (300 µmol/l), the experiments were repeated to assess the EDHF-mediated relaxation response to bradykinin. Results: HES 6 mg/ml induced a significant (p < 0.01) reduction in EDR (n = 8). After incubation with HES and nitric oxide blockage with N-nitro-L-arginine, the relaxation response was reduced especially for the bradykinin concentrations of 10^–6 mol/l (p < 0.05) and 10^–5 mol/l (p < 0.01). Conclusion: For the clinically relevant concentration of 6 mg/ml HES, a significant reduction in EDR and the EDHF can be found in epicardial coronary arteries of the pig.