Cs. Venugopal et al., In vitro pharmacologic effect of two endothelin-1 antagonists on equine colonic arteries and veins, AM J VET RE, 62(2), 2001, pp. 154-159
Objective-To evaluate the effectiveness of 2 potential endothelin (ET)-1 an
tagonists in blocking the contractile responses of equine colonic vessels t
o increasing concentrations of ET-1.
Sample Population-Mesenteric vessels from 6 clinically healthy horses. Proc
edure-Colonic vessels (arterial and venous rings) were placed in organ bath
s with oxygenated Tyrode solution at 37 C. Each was attached to a force tra
nsducer interfaced with a polygraph, and 2 g of tension was applied and equ
ilibrated for 45 minutes. Then, B-1 (PD 142893) and B-2 (PD 145065) ET-1 an
tagonists were tested. One ring from each vessel type was used as a control
for determining concentration-response relationships of ET-1 (10(-10) to 1
0(-6)M). Three rings of each vessel type were incubated with 3 concentratio
ns of each antagonist (10(-7), 10(-6) and 10(-5)M) for 30 minutes before ET
induced contractions were determined. The maximum contractile response and
pA(2) values were determined.
Results-Vessels contracted in a concentration-dependent manner to ET-1. Art
eries responded slowly but reached greater contractions. Veins responded im
mediately with sustained contractions. Both antagonists inhibited contracti
ons In a concentration-dependent manner with significant differences at 10(
-6) and 10(-5)M for arteries and 10(-5)M for veins. Complete blockade of co
ntractions was observed with B-2 (10(-5)M). The pA(2) values for B-1 were 8
.26 and 6.82 for arteries and veins, respectively, whereas they were 8.25 a
nd 7.21 for 8-2.
Conclusion end Clinical Relevance-Both antagonists effectively blocked ET-1
-induced contractions of equine colonic vessels. Because B-2 is water solub
le and caused complete blockade at 10(-5)M, it appears to be the preferred
antagonist.