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In vitro evaluation of the contractile response to endothelin-1 of the circular and longitudinal myometrial layers of the uterine horn of nongravid mares

Honor A. Walesby DVM, MS1, Changaram S. Venugopal BVSc, PhD2, Giselle Hosgood BVSc, PhD3, Susan C. Eades DVM, PhD4, and Rustin M. Moore DVM, PhD5
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  • 1 Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 2 Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 3 Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 4 Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 5 Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.

Abstract

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.

Sample Population—Uteruses from 10 nongravid mares in anestrus.

Procedure—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 10–5M) of BQ-123, IRL- 1038, or BQ-123 and IRL-1038 before concentrationresponse curves to ET-1 were generated. Contractile response to cumulative concentrations of ET-1 (10–9 to 10–6M) 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 and Clinical Relevance—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. (Am J Vet Res 2005;66:1094–1100)

Abstract

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.

Sample Population—Uteruses from 10 nongravid mares in anestrus.

Procedure—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 10–5M) of BQ-123, IRL- 1038, or BQ-123 and IRL-1038 before concentrationresponse curves to ET-1 were generated. Contractile response to cumulative concentrations of ET-1 (10–9 to 10–6M) 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 and Clinical Relevance—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. (Am J Vet Res 2005;66:1094–1100)