Effects of hydroxyethyl starch, gelatin and dextran on endothelium-derived relaxation in porcine coronary arteries.
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).


CONCLUSIONS
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.
Dagtekin
Oguzhan
O
Department of Anaesthesiology and Intensive Care Medicine, University of Cologne, Cologne, Germany. oguzhan.dagtekin@uk-koeln.de
Klisa
Maite Ann-Katrin
MA
Gerbershagen
Hans Jürgen
HJ
Marcus
Hanke
H
Krep
Henning
H
Teschendorf
Peter
P
Fischer
Jürgen Hartmut
JH
D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D003911:Dextrans / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005780:Gelatin / Q000008:administration & dosage / Q000494:pharmacology*; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D013552:Swine
D001685:Biological Factors; D003911:Dextrans; D006895:Hydroxyethyl Starch Derivatives; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; D005780:Gelatin; D007213:Indomethacin