RESUMEN

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, 10⁻¹° 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.

Asunto(s)

Vasos Coronarios/efectos de los fármacos , Dextranos/farmacología , Gelatina/farmacología , Derivados de Hidroxietil Almidón/farmacología , Animales , Factores Biológicos/metabolismo , Vasos Coronarios/metabolismo , Dextranos/administración & dosificación , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Gelatina/administración & dosificación , Derivados de Hidroxietil Almidón/administración & dosificación , Técnicas In Vitro , Indometacina/farmacología , Óxido Nítrico/metabolismo , Nitroarginina , Porcinos