Response of hamster cheek pouch microcirculation to endothelin and endothelin receptor antagonists

Our goal was to examine the effects of endothelin-1 and endothelin-3 on hamster cheek pouch arterioles in vivo in the absence and presence of endothelin receptor antagonists. Endothelin-1 (0.1, 1.0 and 10 pM) and endothelin-3 (0.1 and 1.0 nM) produced dose-related constriction of cheek pouch arterioles which was inhibited by the endothelin ETAB receptor antagonist PD 142893 (Ac-D-Dip-Leu-Asp-Ile-Ile-Trp) and endothelin ETA receptor antagonist PD 147953 [FR 139317: (hexahydro-1H-azepinyl)carbonyl-Leu-(N-Me)-D-Trp- D-2-Pya]. The thromboxane analogue, U-46619 (0.1 and 1.0 nM) also produced dose-related constriction of cheek pouch arterioles, but in contrast to endothelin-1 and endothelin-3 this vasoconstriction was not abolished by endothelin receptor antagonists. These findings suggest that endothelin-1 and endothelin-3 produce marked constriction of cheek pouch arterioles which appears to be mediated by activation of endothelin ETA receptors.