Hydroxyethyl starch inhibits endothelium-derived relaxation in porcine coronary arteries.
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 micromol/l) was added in all measurements to eliminate prostacyclin effects. Prostaglandin F2alpha (10 micromol/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 micromol/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).


CONCLUSIONS
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.
Dagtekin
Oguzhan
O
Department of Anaesthesiology, University of Cologne, Cologne, Germany. oguzhan.dagtekin@uk-koeln.de
Krep
Henning
H
Fischer
Jürgen Hartmut
JH
D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin; D009569:Nitric Oxide / Q000096:biosynthesis; D019335:Nitroarginine; D010952:Plasma Substitutes / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D001685:Biological Factors; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; D015237:Dinoprost; D001920:Bradykinin; D007213:Indomethacin