Effects of Hydroxyethyl Starch, Gelatin and Dextran on Endothelium-Derived Relaxation in Porcine Coronary Arteries

Abstract

Background: In a pilot study we could show that hydroxyethyl starch (HES) induced a significant reduction of endothelium-dependent relaxation (EDR) and the endothelium-derived hyperpolarizing factor (EDHF). In this follow-up study we investigated whether this effect of HES was dose-dependent and whether it could be replicated with other colloids like dextran (DX) and gelatin (GL). Methods: Rings of fresh porcine coronary arteries were consecutively tested with or without HES, DX or GL (5, 10, or 20 mg/ml). Indomethacin was added in all measurements to eliminate prostacyclin effects. Prostaglandin F₂α was used for contraction and bradykinin (BK, 10^–10 to 10^–5M) for inducing EDR. After blocking nitric oxide (NO) by N-nitro-L-arginine (L-NNA), the experiments were repeated to assess the EDHF-mediated relaxation response to BK. Results: HES induced a reduction in EDR for the BK concentrations of 10^–8 and 10^–7M (n = 10; p < 0.05). After NO blockage with L-NNA, the relaxation response was reduced especially for the BK concentrations of 10^–6 and 10^–5M (p < 0.05). GL showed a reduction in EDR with or without NO blockage with L-NNA especially for the BK concentrations of 10^–6 and 10^–5M (n = 14; p < 0.05). DX induced a significant reduction in EDR for the BK concentrations of 10^–7 and 10^–6M (n = 12; p < 0.05). After NO blockage with L-NNA, the relaxation response was reduced especially for the BK concentrations of 10^–6 and 10^–5M (p < 0.05). Conclusion: For clinically relevant concentrations of HES, DX and GL a significant reduction in both NO-induced and NO-/prostacyclin-independent EDR can be found in epicardial coronary arteries of the pig.