Endothelin receptor alterations in equine airway hyperreactivity.
The purpose of this study was to evaluate the role of endothelin-1 (ET-1) and its receptors in the airway hyperreactivity of horses with obstructive pulmonary disease associated with summer pasture (SPAOPD). The right diaphragmatic lobe of the lung of 8 clinically healthy (unaffected) and 8 SPAOPD-affected horses was collected immediately after euthanasia. Bronchial rings (4 mm wide) were prepared and mounted in organ baths and attached to force transducers interfaced with a polygraph. Four rings were used to study each ET-1 receptor; 1 ring served as the control, and the other 3 were incubated with 10(-9), 10(-7), or 10(-5) M of either BQ-123, an ET(A)-receptor antagonist, or IRL-1038, an ET(B)-receptor antagonist. Cumulative concentrations (10(-8.5) to 10(-6) M) of ET-1 were applied to all rings. Using pooled pulmonary tissue from different regions of the lung, we performed a reverse-transcription polymerase chain reaction (RT-PCR) to determine ET(B)-receptor gene expression. Although ET-1 caused concentration-dependent bronchial ring contraction in both groups of horses, the rings of SPAOPD-affected horses had significantly greater contraction than the rings of unaffected horses. Whereas ET(A)-receptor blockade significantly increased the response to ET-1 in unaffected horses, ET(B)-receptor blockade significantly decreased the response in affected horses. The pA2 values showed a nonsignificant decrease in ET(A)-receptor affinity and a significant increase in ET(B)-receptor affinity in affected horses compared with unaffected horses. The ET(B)-receptor mRNA expression of the pooled pulmonary tissue showed a nonsignificant increase in affected horses compared with unaffected horses. The airway hyperreactivity to ET-1 observed in the bronchial rings from the affected horses appears to be due in part to activation of pulmonary ET(B) receptors, which appear to be inactive in unaffected horses.
Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA. cvenugopal@vetmed.lsu.edu
Changaram S
CS
Venugopal
Sumanth
S
Polikepahad
Earnestine P
EP
Holmes
John Vanden
JV
Heuvel
Tara L
TL
Leas
Rustin M
RM
Moore
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015870:Gene Expression; D006734:Horse Diseases / Q000378:metabolism* / Q000503:physiopathology; D006736:Horses; D008173:Lung Diseases, Obstructive / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D009924:Organ Culture Techniques / Q000662:veterinary; D006109:Poaceae; D017466:Receptors, Endothelin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D012621:Seasons
D019332:Endothelin-1; D017466:Receptors, Endothelin