AJP - Gastrointestinal and Liver Physiology, Vol 266, Issue 2 311-G317, Copyright © 1994 by American Physiological Society
Phosphoramidon attenuates big endothelin-1-induced vasoconstriction in canine stomach
J. G. Wood, Z. Y. Yan, J. M. Davis and L. Y. Cheung
Department of Surgery, University of Kansas Medical Center, Kansas City 66160.
We compared the effects of endothelin-1 and its precursor, big
endothelin-1, on vascular resistance of a blood-perfused ex vivo stomach
segment of chloralose-anesthetized dogs. In separate groups of dogs,
endothelin-1 or big endothelin-1 was infused intra-arterially directly to
the gastric segment. Endothelin-1 caused statistically significant
dose-related increases in gastric vascular resistance at final blood
concentrations of 0.15-10 nM. Although each dose was given for only 5 min,
endothelin-1 at concentrations > 0.6 nM caused sustained responses with
vascular resistance remaining above control values for approximately 45-90
min. In contrast, however, big endothelin-1 caused a small but
statistically significant vasoconstriction only at the highest
concentration (10 nM). In other experiments, using 15-min peptide
infusions, we found that pretreatment with phosphoramidon, an inhibitor of
endothelin-converting enzyme, markedly reduced response to big endothelin-1
but not to endothelin-1. Our results demonstrate that endothelin-1, but not
big endothelin-1, is a potent vasoconstrictor of the canine gastric
microcirculation. In addition, it appears that big endothelin-1 is degraded
to endothelin-1 in the stomach by a phosphoramidon-sensitive
metalloproteinase.
