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  • Title: Effects of hydroxyethyl starch, gelatin and dextran on endothelium-derived relaxation in porcine coronary arteries.
    Author: Dagtekin O, Klisa MA, Gerbershagen HJ, Marcus H, Krep H, Teschendorf P, Fischer JH.
    Journal: Pharmacology; 2010; 86(5-6):267-72. PubMed ID: 20980779.
    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 10⁻⁵ M) 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 10⁻⁷ M (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 10⁻⁵ M (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 10⁻⁵ M (n = 14; p < 0.05). DX induced a significant reduction in EDR for the BK concentrations of 10⁻⁷ and 10⁻⁶ M (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 10⁻⁵ M (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.
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