AJP - Gastrointestinal and Liver Physiology, Vol 262, Issue 6 977-G982, Copyright © 1992 by American Physiological Society
Relative potency of endothelin analogues on changes in gastric vascular resistance
J. G. Wood, Z. Y. Yan and L. Y. Cheung
Department of Surgery, University of Kansas Medical Center, Kansas City 66160.
The purpose of this study was to examine the effects of several endothelin
analogues on the gastric microcirculation. We measured changes in vascular
resistance of an ex vivo gastric segment of chloralose-anesthetized dogs.
Changes in luminal pressure were used to quantitate contractile force.
Graded doses of endothelin-2 (ET-2), endothelin-3 (ET-3),
[Ala3,11]endothelin (Ala-ET), and the COOH-terminal hexapeptide (ET-C) were
infused intra-arterially to the stomach. ET-2 and Ala-ET produced
dose-related sustained increases in vascular resistance (10(-10) to 10(-8)
M), with Ala-ET less potent than ET-2. In contrast, ET-3 was a weak
vasoconstrictor while ET-C had no significant effects. There were no
detectable changes in filtration with any of these analogues. However, the
force of gastric contractions was significantly attenuated by both ET-2 and
Ala-ET in a dose-dependent manner. We found that endothelin analogues
produced sustained vasoconstriction of the gastric segment with a potency
order of ET-2 greater than Ala-ET-3 much greater than ET-C. Our results
suggest that endothelin analogues are potent vasoconstrictors but have
little effect on filtration across the gastric vasculature.
