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

Changaram S. VenugopalEquine Health Studies Program, Departments of Veterinary Physiology, Pharmacology & Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Earnestine P. HolmesEquine Health Studies Program, Departments of Veterinary Physiology, Pharmacology & Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Catherine E. KochEquine Health Studies Program, Departments of Veterinary Physiology, Pharmacology & Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Lee Ann CurtisVeterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Ashley S. HolmEquine Health Studies Program, Departments of Veterinary Physiology, Pharmacology & Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Rustin M. MooreEquine Health Studies Program, Departments of Veterinary Physiology, Pharmacology & Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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 DVM, PhD

Abstract

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 10–6 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 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 10–5 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.

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 10–5 M, it appears to be the preferred antagonist. (Am J Vet Res 2001;62:154–159)

Abstract

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 10–6 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 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 10–5 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.

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 10–5 M, it appears to be the preferred antagonist. (Am J Vet Res 2001;62:154–159)