In vitro pharmacologic effect of two endothelin-1 antagonists on equine colonic arteries and veins

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.