Objective—To evaluate the effectiveness of 2 potential
endothelin (ET)-1 antagonists in blocking the contractile
responses of equine colonic vessels to
increasing concentrations of ET-1.
Sample Population—Mesenteric vessels from 6
clinically healthy horses.
Procedure—Colonic vessels (arterial and venous
rings) were placed in organ baths with oxygenated
Tyrode solution at 37 C. Each was attached to a force
transducer interfaced with a polygraph, and 2 g of
tension was applied and equilibrated for 45 minutes.
Then, B-1 (PD 142893) and B-2 (PD 145065) ET-1
antagonists were tested. One ring from each vessel
type was used as a control for determining concentration-
response relationships of ET-1 (10–10 to 10–6M).
Three rings of each vessel type were incubated with
3 concentrations of each antagonist (10–7, 10–6, and 10
–5M) for 30 minutes before ET induced contractions
were determined. The maximum contractile
response and pA2 values were determined.
Results—Vessels contracted in a concentrationdependent
manner to ET-1. Arteries responded slowly
but reached greater contractions. Veins responded
immediately with sustained contractions. Both antagonists
inhibited contractions in a concentrationdependent
manner with significant differences at 10–6
and 10–5M for arteries and 10–5M for veins. Complete
blockade of contractions was observed with B-2
(10–5M). The pA2 values for B-1 were 8.26 and 6.82 for
arteries and veins, respectively, whereas they were
8.25 and 7.21 for B-2.
Conclusion and Clinical Relevance—Both antagonists
effectively blocked ET-1-induced contractions of
equine colonic vessels. Because B-2 is water soluble
and caused complete blockade at 10–5M, it appears to
be the preferred antagonist. (Am J Vet Res 2001;62:154–159)