In vitro evaluation of the contractile response to endothelin-1 of the circular and longitudinal myometrial layers of the uterine horn of nongravid mares.
OBJECTIVE
To characterize the in vitro response of circular and longitudinal myometrial layers of the uterine horn (CMLH and LMLH, respectively) of horses to endothelin (ET)-1 by use of specific ETA (BQ-123) and ETB (IRL-1038) receptor antagonists.


METHODS
Uteruses from 10 nongravid mares in anestrus.


METHODS
Muscle strips from the CMLH and LMLH were suspended in tissue baths and connected to force-displacement transducers interfaced with a polygraph. Strips were incubated for 45-minute intervals with no antagonist (control specimens), and 3 concentrations (10(-9), 10(-7), and 10(-5)M) of BQ-123, IRL-1038, or BQ-123 and IRL-1038 before concentration-response curves to ET-1 were generated. Contractile response to cumulative concentrations of ET-1 (10(-9) to 10(-6)M) was quantified by measuring change in the area under the curve (AUC) for the 3-minute period after each ET-1 dose.


RESULTS
ET-1 caused concentration-dependent contraction of the CMLH and LMLH specimens. Application of BQ-123 decreased AUC values for both layers. Application of IRL-1038 increased the AUC value for LMLH specimens but did not affect the CMLH value. The combination of BQ-123 and IRL-1038 decreased the AUC value for LMLH tissue and increased that for CMLH tissue.


CONCLUSIONS
ET-1 causes contraction of the CMLH and LMLH in nongravid horses. In both layers, ETA receptors mediate contraction but the role of ETB receptors remains unclear. In the LMLH, ETA receptors have a dominant role; the presence of another receptor or receptor subtype within this layer is suggested. These findings support a physiologic role for ET-1 in uterine contractility.
Walesby
Honor A
HA
Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410, USA.
Venugopal
Changaram S
CS
Hosgood
Giselle
G
Eades
Susan C
SC
Moore
Rustin M
RM
D000818:Animals; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D006736:Horses / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); C072247:cyclo(Trp-Asp-Pro-Val-Leu)