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 antagonists in blocking the contractile responses of equine colonic vessels to increasing concentrations of ET-1.


METHODS
Mesenteric vessels from 6 clinically healthy horses.


METHODS
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(-6)M). Three rings of each vessel type were incubated with 3 concentrations 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 pA2 values were determined.


RESULTS
Vessels contracted in a concentration-dependent manner to ET-1. Arteries responded slowly but reached greater contractions. Veins responded immediately with sustained contractions. Both antagonists inhibited contractions 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 contractions was observed with B-2 (10(-5)M). 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.


CONCLUSIONS
Both antagonists effectively blocked ET-1-induced contractions of equine colonic vessels. Because B-2 is water soluble and caused complete blockade at 10(-5) M, it appears to be the preferred antagonist.
Venugopal
C S
CS
Equine Health Studies Program, Department of Veterinary Physiology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803, USA.
Holmes
E P
EP
Koch
C E
CE
Curtis
L A
LA
Holm
A S
AS
Moore
R M
RM
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D003106:Colon / Q000098:blood supply* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006736:Horses / Q000502:physiology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014680:Veins / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D009842:Oligopeptides; C076213:PD 142893; C082887:PD 145065