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 o n hamster cheek pouch arterioles in vivo in the absence and presence o f endothelin receptor antagonists. Endothelin-1 (0.1, 1.0 and 10 pM) a nd endothelin-3 (0.1 and 1.0 nM) produced dose-related constriction of cheek pouch arterioles which was inhibited by the endothelin ET(AB) r eceptor antagonist PD 142893 (Ac-D-Dip-Leu-Asp-Ile-Ile-Trp) and endoth elin ET(A) receptor antagonist PD 147953 [FR 139317: ydro-1H-azepinyl) carbonyl-Leu-(N-Me)-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 vaso constriction was not abolished by endothelin receptor antagonists. The se findings suggest that endothelin-1 and endothelin-3 produce marked constriction of cheek pouch arterioles which appears to be mediated by activation of endothelin ET(A) receptors.