Objective—To immunohistochemically determine the expression of endothelin (ET) receptors in bronchial smooth muscle and epithelium of healthy horses and horses affected by summer pasture-associated obstructive pulmonary disease (SPAOPD).
Sample Population—Tissue specimens obtained from 8 healthy and 8 SPAOPD-affected horses.
Procedure—Horses were examined and assigned to healthy and SPAOPD groups. Horses were then euthanatized, and tissue specimens containing bronchi of approximately 4 to 8 mm in diameter were immediately collected from all lung lobes, fixed in zinc-formalin solution for 12 hours, and embedded in paraffin. Polyclonal primary antibodies against ET-A or ET-B receptors at a dilution of 1:200 and biotinylated IgG secondary antibodies were applied to tissue sections, followed by the addition of an avidin-biotin immunoperoxidase complex. Photographs of the stained slides were digitally recorded and analyzed by use of image analysis software to determine the intensity of staining. Two-way ANOVA was used for statistical analysis.
Results—The left diaphragmatic lung lobe of SPAOPD-affected horses had a significantly greater area of bronchial smooth muscle that immunostained for ET-A, compared with that for healthy horses. All lung lobes of SPAOPD-affected horses, except for the right diaphragmatic lobe, had significantly greater staining for ET-B receptors in bronchial smooth muscle, compared with results for healthy horses.
Conclusions and Clinical Relevance—This study revealed overexpression of ET-A and, in particular, ETB receptors in the bronchial smooth muscle of SPAOPD-affected horses, which suggested upregulation of these receptors. These findings improve our understanding of the role of ET-1 in the pathogenesis of SPAOPD.
Objective—To evaluate 3 neurokinin-2 (NK2) receptor
antagonists on the basis of their ability to block neurokinin
A (NKA)-induced contractile responses in various
regions of the guinea pig respiratory tract.
Animals—48 clinically normal guinea pigs.
Procedure—After euthanasia, the trachea and lungs
were removed en bloc. The spirally cut trachea was
divided into lower, middle, and upper portions. The
main bronchus was spirally cut. A lung strip was cut
from the edge of the lung. Tissue strips were mounted
in organ baths containing Tyrode solution at 37°C
and attached to force transducers interfaced with a
polygraph. Lung strips were set at a tension of 1 g;
other tissue strips were set at 2 g. After 45 minutes
of equilibration, cumulative concentration-response
(CR) relationships to graded concentrations of NKA
were determined. In the treatment groups, tissues
were incubated (30 minutes) with antagonists (MEN
10376, SR 48968, and SR 144190) at 3 concentrations
(10–9, 10–7, and 10–5M) before CR relationships were
determined. Effectiveness of SR 48968 against NKA
was also tested in vivo.
Results—Lung strips failed to contract, but all others
responded in a concentration-dependent manner.
Bronchial spirals were most sensitive. SR 48968 had
the highest pA2 value and effectively blocked NKA.
Conclusions and Clinical Relevance—The bronchial
region where airflow resistance is high was the most
sensitive to NKA, suggesting the importance of NKA
in bronchoconstriction. Nonpeptide antagonists (SR
48968 and SR 144190) were more potent than the
peptide antagonist (MEN 10376), indicating their
greater therapeutic potential as antiasthmatic agents.
( Am J Vet Res 2004;65:984–991)